ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.188T>C (p.Val63Ala) (rs727504309)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154364 SCV000204027 uncertain significance not specified 2014-02-01 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Val63Ala va riant in GJB2 has been previously reported in one individual with hearing loss w ho carried a second pathogenic GJB2 variant and was not identified in 588 contro l chromosomes (Tang, 2006). Computational analyses (conservation, AlignGVGD, Pol yPhen2, and SIFT) suggest that the Val63Ala variant may impact the protein, thou gh this information is not predictive enough to determine pathogenicity. In summ ary, the clinical significance of this variant cannot be determined with certain ty; however, based on its presence in an individual with hearing loss who carrie d a second GJB2 variant and the computational and conservation data suggestive o f an impact to the protein, we would lean towards a more likely pathogenic role.
Athena Diagnostics Inc RCV000711348 SCV000841700 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765115 SCV000896337 uncertain significance Deafness, autosomal recessive 1A; Mutilating keratoderma; Hystrix-like ichthyosis with deafness; Keratitis-ichthyosis-deafness syndrome, autosomal dominant; Palmoplantar keratoderma-deafness syndrome; Knuckle pads, deafness AND leukonychia syndrome; Deafness, autosomal dominant 3a; Deafness, X-linked 2 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154364 SCV000917456 uncertain significance not specified 2017-09-11 criteria provided, single submitter clinical testing Variant summary: The GJB2 c.188T>C (p.Val63Ala) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 5/121934 control chromosomes at a frequency of 0.000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic GJB2 variant (0.025). The variant has been reported in affected individuals in the literature, without evidence for causality. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
GeneDx RCV000711348 SCV001781027 uncertain significance not provided 2019-10-23 criteria provided, single submitter clinical testing Observed with a second GJB2 variant in an individual with hearing loss in published literature, however, the phase of these variants is unknown (Tang et al., 2003); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24774219, 30245029, 25388846, 17041943, 19366456)
Natera, Inc. RCV001271875 SCV001453348 uncertain significance Deafness, autosomal recessive 1A 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.