ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.385G>A (p.Glu129Lys) (rs397516875)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037849 SCV000061511 uncertain significance not specified 2013-02-01 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Glu129Lys varia nt in GJB2 has been reported in 5 individuals with sensorineural hearing loss (K enna 2001, Dalamon 2005, Najmabadi 2005, Primignani 2009, Putcha 2007). Only 1 o f these individuals had a variant on the other allele, though the one other vari ant (Ala40Gly) is also of unknown significance. In another family, both the fath er and proband had unilateral high frequency sensorineural hearing loss raising the possibility of a dominant pattern of inheritance (Kenna 2001) though this is not consistent with the other 4 cases in the literature. This variant has not b een identified in large and broad ethnically-matched populations by NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Computational analyses (b iochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, additional data is needed to determine the clinical significance of this variant; however, given th e absence of clear disease-causing variants on the second allele of any of the r eported case, we would lean towards a more likely benign interpretation.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000730888 SCV000858655 uncertain significance not provided 2017-12-12 criteria provided, single submitter clinical testing

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