ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.677T>G (p.Val226Gly) (rs773846324)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel, RCV000710340 SCV000840534 uncertain significance Nonsyndromic hearing loss and deafness 2018-09-14 reviewed by expert panel curation The c.677T>G (p.Val226Gly) variant has been identified in the heterozygous state in one individual with sensorineural hearing loss and one individual with breast or ovarian cancer in the literature (PS4 not met; 17666888 27153395). The allele frequency of the p.Val226Gly variant in the GJB2 gene is 0.003% (1/343458) of Latino chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2). In summary, this variant meets criteria to be classified as a variant of uncertain clinical significance for autosomal recessive nonsyndromic hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2.
Athena Diagnostics Inc RCV000516262 SCV000613524 uncertain significance not specified 2016-09-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000516262 SCV000731317 uncertain significance not specified 2017-02-28 criteria provided, single submitter clinical testing The p.Val226Gly variant in GJB2 has been reported in the heterozygous state in o ne individual with hearing loss (Putcha 2007). This variant has been identified in 1/11448 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs773846324). Although this variant has been seen in the general population, its frequency is not high enough to rule out a patho genic role. Computational prediction tools and conservation analysis do not prov ide strong support for or against an impact to the protein. In summary, the clin ical significance of the p.Val226Gly variant is uncertain.
Counsyl RCV000664825 SCV000788843 uncertain significance Deafness, autosomal recessive 1A 2017-01-04 criteria provided, single submitter clinical testing

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