ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.576del (p.Val193fs) (rs747847191)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798022 SCV000937614 pathogenic not provided 2018-12-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GJB2 gene (p.Val193Cysfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acids of the GJB2 protein. This variant is present in population databases (rs747847191, ExAC 0.002%). This variant has been observed in several individuals affected with non-syndromic hearing loss (PMID: 12497637, 20553101, 17666888). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the p.Asn206 amino acid residue in GJB2. Other variant(s) that disrupt this residue have been observed in individuals with GJB2-related conditions (PMID: 12172394, 14985372, 15070423, 15967879), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000798022 SCV001476381 pathogenic not provided 2020-02-21 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.

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