ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.299A>T (p.His100Leu) (rs1422767764)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781416 SCV000919429 likely pathogenic Deafness, autosomal recessive 1A 2018-08-02 criteria provided, single submitter clinical testing Variant summary: GJB2 c.299A>T (p.His100Leu) results in a non-conservative amino acid change located in the Connexin, N-terminal domain (IPR013092) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 31172 control chromosomes (gnomAD and publication data). The variant, c.299A>T, has been reported in the literature in individuals affected with Non-Syndromic Hearing Loss (Primignani 2009, Du 2014). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Kim 2016). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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