GenVue Discovery
GenVue Discovery
Curation
Below are rare variants (frequency less than 1%) that were submitted to ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.
Gene:
GJB2
Variant:
c.71G>A
(p.Trp24Ter)
rsID: rs104894396
Ref Allele: C
Alt Allele: T
Freq: 0.0399%rare
CADD: 42
ClinVar Submissions (17)
DFNX2, also known as DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss and a pathognomonic temporal bone deformity that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn, resulting in a perilymphatic fluid 'gusher' during stapes surgery (summary by de Kok et al., 1995 and Song et al., 2010). See also choroideremia, deafness, and mental retardation (303110), a contiguous gene deletion syndrome involving the POU3F4 and CHM (300390) genes on Xq21; isolated choroideremia (303100) is caused by mutation in the CHM gene.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Nonsyndromic hearing loss and deafness, DFNA3 is characterized by pre- or postlingual, mild-to-profound progressive high-frequency sensorineural hearing impairment. Affected individuals have no other associated medical findings.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Nonsyndromic hearing loss and deafness, DFNA3 is characterized by pre- or postlingual, mild-to-profound progressive high-frequency sensorineural hearing impairment. Affected individuals have no other associated medical findings.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
A decreased magnitude of the sensory perception of sound. [HPO:probinson]
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
A partial or complete loss of hearing in one or both ears. It is classified as conductive, sensory, or central.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Hystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds.The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Bart-Pumphrey syndrome is characterized by nail and skin abnormalities and hearing loss.People with Bart-Pumphrey syndrome typically have a white discoloration of the nails (leukonychia); the nails may also be thick and crumbly. Affected individuals often have wart-like (verrucous) skin growths called knuckle pads on the knuckles of the fingers and toes. They may also have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). The skin abnormalities generally become noticeable during childhood.The hearing loss associated with Bart-Pumphrey syndrome ranges from moderate to profound and is typically present from birth (congenital).The signs and symptoms of this disorder may vary even within the same family; while almost all affected individuals have hearing loss, they may have different combinations of the other associated features.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin.In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss.The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs. The ichthyosis is usually mild, and there may also be mild reddening of the skin (erythroderma). Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body.Nonsyndromic hearing loss can be classified in several different ways. One common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial (which does not have a special designation). Each of these types of hearing loss includes multiple subtypes. DFNA, DFNB, and DFNX subtypes are numbered in the order in which they were first described. For example, DFNA1 was the first type of autosomal dominant nonsyndromic hearing loss to be identified.The characteristics of nonsyndromic hearing loss vary among the different types. Hearing loss can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The term "deafness" is often used to describe severe-to-profound hearing loss. Hearing loss can be stable, or it may be progressive, becoming more severe as a person gets older. Particular types of nonsyndromic hearing loss show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.Most forms of nonsyndromic hearing loss are described as sensorineural, which means they are associated with a permanent loss of hearing caused by damage to structures in the inner ear. The inner ear processes sound and sends the information to the brain in the form of electrical nerve impulses. Less commonly, nonsyndromic hearing loss is described as conductive, meaning it results from changes in the middle ear. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly a type called DFNX2, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.Depending on the type, nonsyndromic hearing loss can become apparent at any time from infancy to old age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 17
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 13:20763650
OMIM Allelic Variant: 121011.0003
Expert Reviewed Clinically Significant Pathogenic
Hetero
Gene:
WFS1
Variant:
c.577A>C
(p.Lys193Gln)
rsID: rs41264699
Ref Allele: A
Alt Allele: C
Freq: 0.2196%rare
CADD: 23.6
ClinVar Submissions (6)
Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.
Last Evaluated: Apr 10, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:6293040
Last Evaluated: Apr 10, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:6293040
Last Evaluated: Apr 10, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:6293040
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Apr 10, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:6293040
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 10, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:6293040
Benign/Likely benign
Hetero
Gene:
MYO3A
Variant:
c.3133G>A
(p.Val1045Met)
rsID: rs35447806
Ref Allele: G
Alt Allele: A
Freq: 0.2995%rare
CADD: 27.7
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 01, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 10:26457662
Benign
Hetero
Gene:
FOLR1
Variant:
c.493+2T>C
rsID: rs144637717
Ref Allele: T
Alt Allele: C
Freq: 0.3395%rare
CADD: 25.2
ClinVar Submissions (8)
This is an autosomal recessive disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function (Steinfeld et al., 2009).
Last Evaluated: Nov 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:71906793
Last Evaluated: Nov 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:71906793
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:71906793
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:71906793
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
BRCA2
Variant:
c.9976A>T
(p.Lys3326Ter)
rsID: rs11571833
Ref Allele: A
Alt Allele: T
Freq: 0.4393%rare
CADD: 36
ClinVar Submissions (34)
Ovarian cancer is a disease that affects women. In this form of cancer, certain cells in the ovary become abnormal and multiply uncontrollably to form a tumor. The ovaries are the female reproductive organs in which egg cells are produced. In about 90 percent of cases, ovarian cancer occurs after age 40, and most cases occur after age 60.The most common form of ovarian cancer begins in epithelial cells, which are the cells that line the surfaces and cavities of the body. These cancers can arise in the epithelial cells on the surface of the ovary. However, researchers suggest that many or even most ovarian cancers begin in epithelial cells on the fringes (fimbriae) at the end of one of the fallopian tubes, and the cancerous cells migrate to the ovary.Cancer can also begin in epithelial cells that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, resembles epithelial ovarian cancer in its origin, symptoms, progression, and treatment. Primary peritoneal cancer often spreads to the ovaries. It can also occur even if the ovaries have been removed. Because cancers that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one of these structures to the others, they are often difficult to distinguish. These cancers are so closely related that they are generally considered collectively by experts.In about 10 percent of cases, ovarian cancer develops not in epithelial cells but in germ cells, which are precursors to egg cells, or in hormone-producing ovarian cells called granulosa cells.In its early stages, ovarian cancer usually does not cause noticeable symptoms. As the cancer progresses, signs and symptoms can include pain or a feeling of heaviness in the pelvis or lower abdomen, bloating, feeling full quickly when eating, back pain, vaginal bleeding between menstrual periods or after menopause, or changes in urinary or bowel habits. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a woman has ovarian cancer.In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If ovarian cancer spreads, cancerous tumors most often appear in the abdominal cavity or on the surfaces of nearby organs such as the bladder or colon. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.Some ovarian cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary ovarian cancers tend to develop earlier in life than non-inherited (sporadic) cases.Because it is often diagnosed at a late stage, ovarian cancer can be difficult to treat; it leads to the deaths of about 14,000 women annually in the United States, more than any other gynecological cancer. However, when it is diagnosed and treated early, the 5-year survival rate is high.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 02, 2018
Review Status: reviewed by expert panel
Number of Submitters: 34
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32972626
Expert Reviewed Clinically Significant Benign
Hetero
Gene:
BRCA2
Variant:
c.9257-276G>A
rsID: rs11571815
Ref Allele: G
Alt Allele: A
Freq: 0.4593%rare
CADD: 2.73
ClinVar Submissions (1)
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.
Last Evaluated: Jan 12, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 13:32968550
Expert Reviewed Benign
Hetero
Gene:
ERCC1
Variant:
c.225G>A
(p.Thr75=)
rsID: rs3212947
Ref Allele: C
Alt Allele: T
Freq: 0.4992%rare
CADD: 0.853
ClinVar Submissions (1)
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 19:45924532
Conflicting/Uncertain
Hetero
Gene:
FREM2
Variant:
c.4319C>A
(p.Thr1440Lys)
rsID: rs79048205
Ref Allele: C
Alt Allele: A
Freq: 0.5192%rare
CADD: 27.8
ClinVar Submissions (1)
Fraser syndrome is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract (summary by van Haelst et al., 2008). Genetic Heterogeneity of Fraser Syndrome Fraser syndrome-2 (FRASRS2) is caused by mutation in the FREM2 gene (608945) on chromosome 13q13, and Fraser syndrome-3 (FRASRS3) is caused by mutation in the GRIP1 gene (604597) on chromosome 12q14. See Bowen syndrome (211200) for a comparable but probably distinct syndrome of multiple congenital malformations.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 13:39265800
Conflicting/Uncertain
Hetero
Gene:
FKBP10
Variant:
c.917+53G>T
rsID: rs141387386
Ref Allele: G
Alt Allele: T
Freq: 0.5391%rare
CADD: 1.28
ClinVar Submissions (1)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: -
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely pathogenic
Assembly: GRCh37
Chromosome/Position: 17:39975704
Clinically Significant Likely pathogenic
Hetero
Gene:
HYDIN
Variant:
c.14857C>T
(p.Arg4953Trp)
rsID: rs79607350
Ref Allele: G
Alt Allele: A
Freq: 0.5591%rare
CADD: 34
ClinVar Submissions (1)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 30, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 16:70843712
Likely benign
Hetero
Gene:
CHMP2B
Variant:
c.-151C>A
rsID: rs77328592
Ref Allele: C
Alt Allele: A
Freq: 0.5791%rare
CADD: 8.651
ClinVar Submissions (1)
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLD mapping to chromosome 3 (600795), caused by mutation in the CHMP2B gene (609512); inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS (105550), caused by mutation in the C9ORF72 gene (614260) on 9p. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:87276522
Likely benign
Hetero
Gene:
SPINK1
Variant:
c.101A>G
(p.Asn34Ser)
rsID: rs17107315
Ref Allele: T
Alt Allele: C
Freq: 0.639%rare
CADD: 0.165
ClinVar Submissions (8)
A disorder characterized by recurrent episodes of pancreatitis that start at a young age. It is caused by mutations in the PRSS1 or SPINK1 genes. Patients are at a high risk of developing pancreatic carcinoma.
Last Evaluated: Jun 23, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity, risk factor
Assembly: GRCh37
Chromosome/Position: 5:147207678
OMIM Allelic Variant: 167790.0001
Last Evaluated: Jun 23, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity, risk factor
Assembly: GRCh37
Chromosome/Position: 5:147207678
OMIM Allelic Variant: 167790.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 23, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 8
Clinical Significance: Conflicting interpretations of pathogenicity, risk factor
Assembly: GRCh37
Chromosome/Position: 5:147207678
OMIM Allelic Variant: 167790.0001
Expert Reviewed Clinically Significant Conflicting/Uncertain
Hetero
Gene:
CUBN
Variant:
c.8741C>T
(p.Ala2914Val)
rsID: rs45551835
Ref Allele: G
Alt Allele: A
Freq: 0.639%rare
CADD: 28.3
ClinVar Submissions (2)
A disorder characterized by the presence of ANEMIA, abnormally large red blood cells (megalocytes or macrocytes), and MEGALOBLASTS.
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 10:16932384
Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA (MGCA2), also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (MGCA3; 258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13, involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (MGCA4; 250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (MGCA5; 610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (MGCA6; 614739), caused by mutation in the SERAC1 gene (614725) on chromosome 6q25, includes deafness, encephalopathy, and a Leigh-like syndrome. Type VII MGCA (MGCA7; 616271), caused by mutation in the CLPB gene (616254) on chromosome 11q13, includes cataracts, neurologic involvement, and neutropenia. Type VIII MCGA (MGCA8; 617248) is caused by mutation in the HTRA2 gene (606441) on chromosome 2p13. Type IX MCGA (MGCA9; 617698) is caused by mutation in the TIMM50 gene (607381) on chromosome 19q13. Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003. Wortmann et al. (2013) proposed a pathomechanism-based classification for 'inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.'
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 10:16932384
Benign/Likely benign
Hetero
Gene:
MED25
Variant:
c.1483-7C>T
rsID: rs2017698
Ref Allele: C
Alt Allele: T
Freq: 0.6789%rare
CADD: 4.859
ClinVar Submissions (2)
Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210). Autosomal recessive forms of CMT are less frequent than the autosomal dominant or X-linked forms. One form of autosomal recessive axonal CMT (CMT2B1; 605588) is caused by mutation in the LMNA gene (150330) on chromosome 1q21.2-q21.3.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50338236
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50338236
Benign
Hetero
Gene:
TTN
Variant:
c.35784G>A
(p.Arg11928=)
rsID: rs56034831
Ref Allele: C
Alt Allele: T
Freq: 0.6989%rare
CADD: 1.444
ClinVar Submissions (7)
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between age 20 months and four years. In the first decade of life, global motor performances are stable or tend to improve. Moderate joint and neck contractures and spinal rigidity may start in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction starts between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179497133
Benign/Likely benign
Hetero
Gene:
DSG4
Variant:
c.1568C>T
(p.Pro523Leu)
rsID: rs34620697
Ref Allele: C
Alt Allele: T
Freq: 0.7987%rare
CADD: 25.2
ClinVar Submissions (2)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 2
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 18:28983529
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 2
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 18:28983529
Conflicting/Uncertain
Hetero
Gene:
CNGB1
Variant:
c.105G>A
(p.Ala35=)
rsID: rs61997250
Ref Allele: C
Alt Allele: T
Freq: 0.8187%rare
CADD: 0.124
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 16:58001086
Conflicting/Uncertain
Hetero
Gene:
PTGER4
Variant:
c.880G>A
(p.Val294Ile)
rsID: rs111866313
Ref Allele: G
Alt Allele: A
Freq: 0.8387%rare
CADD: 8.654
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 17, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 5:40691893
Benign
Hetero
Gene:
RAB3GAP1
Variant:
c.913A>G
(p.Ile305Val)
rsID: rs116775947
Ref Allele: A
Alt Allele: G
Freq: 0.8986%rare
CADD: 9.478
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Sep 01, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 2:135884166
Benign
Hetero
Gene:
MUTYH
Variant:
c.157+30A>G
rsID: rs3219485
Ref Allele: T
Alt Allele: C
Freq: 0.9385%rare
CADD: 2.838
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: -
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 1:45800033
Benign
Hetero
Gene:
POMT1
Variant:
c.1758G>A
(p.Arg586=)
rsID: rs34954751
Ref Allele: G
Alt Allele: A
Freq: 0.9984%rare
CADD: 14.97
ClinVar Submissions (6)
Congenital muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) are characterized by early onset of muscle weakness, usually before ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; Godfrey et al., 2007). Congenital muscular dystrophy-dystroglycanopathies with or without mental retardation (type B) represent the intermediate range of the spectrum of dystroglycanopathies. They are less severe than muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and more severe than limb-girdle muscular dystrophy-dystroglycanopathy (type C; see MDDGC1, 609308). Genetic Heterogeneity of Congenital Muscular Dystrophy-Dystroglycanopathy with or without Mental Retardation (Type B) Congenital muscular dystrophy with mental retardation due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGB2 (613156), caused by mutation in the POMT2 gene (607439); MDDGB3 (613151), caused by mutation in the POMGNT1 gene (606822); MDDGB4 (613152), caused by mutation in the FKTN gene (607440); MDDGB5 (616612), caused by mutation in the FKRP gene (606596); MDDGB6 (608840), caused by mutation in the LARGE gene (603590); and MDDGB14 (615351), caused by mutation in the GMPPB gene (615320).
Last Evaluated: Aug 28, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:134395574
Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951).
Last Evaluated: Aug 28, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:134395574
Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past age 3.Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as "floppy." The muscle weakness worsens over time.Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals.
Last Evaluated: Aug 28, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:134395574
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Aug 28, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:134395574
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 28, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:134395574
Benign
Hetero