ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.560_605dup (p.Cys202Ter) (rs1566528185)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040588 SCV001204171 pathogenic not provided 2019-12-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GJB2 gene (p.Cys202*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acids of the GJB2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with non-syndromic hearing loss (PMID: 23141775). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the GJB2 protein. Other variant(s) that disrupt this region (p.Cys211* and p.Leu213*) have been determined to be pathogenic (PMID: 15150777 , 23141775). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770823 SCV000902321 pathogenic Deafness, autosomal recessive 1A 2019-02-26 no assertion criteria provided case-control

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