GenVue Discovery
GenVue Discovery
Curation
Below are conditions that were reviewed by an expert panel and/or are in the Genetic Testing Registry (GTR) according to ClinVar. The data presented does not diagnose disease and has no guarantees of reporting accuracy. We report heterozygous variants 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:
APOE
Variant:
c.388T>C
(p.Cys130Arg)
rsID: rs429358
Ref Allele: T
Alt Allele: C
Freq: 15.0559%
CADD: 12.64
ClinVar Submissions (3)
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
Last Evaluated: Jan 10, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 3
Clinical Significance: other
Assembly: GRCh37
Chromosome/Position: 19:45411941
OMIM Allelic Variant: 107741.0008
High clinical importance, pathogenic — This is generally known as the ApoE4 allele of ApoE and is associated with increased risk of Alzheimer's. 20-25% of individuals are heterozygous for this variant, and 1-2% are homozygous. Data from Khachaturian et al. suggests an average 7% of all individuals developed Alzheimer's by the age of 80; when this is split by ApoE4 status: 10% of ApoE4 heterozygotes (3% increased attributable risk), 40% of ApoE4 homozygotes (33% increased attributable risk), and 5% of non-carriers (2% decreased attributable risk). Notably, their model suggests 70-75% of people would eventually develop Alzheimer's by the age of 100 regardless of ApoE4 genotype (and 25-30% are resistant, regardless of genotype), but that ApoE4 variants shift the disease onset to occur significantly earlier (4 years earlier for heterozygous carriers, 13 years for homozygotes).
Expert Reviewed Clinically Significant
Hetero
Gene:
CCDC170
Variant:
g.151627231G>A
rsID: rs2046210
Ref Allele: G
Alt Allele: A
Freq: 41.2141%
CADD: 3.559
ClinVar Submissions (1)
Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994).
Last Evaluated: Mar 01, 2014
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Likely pathogenic
Assembly: GRCh37
Chromosome/Position: 6:151948366
Expert Reviewed Clinically Significant Likely pathogenic
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:
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