Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001844223 | SCV000807820 | likely pathogenic | Nonsyndromic Deafness | 2018-03-10 | criteria provided, single submitter | clinical testing | This variant creates a premature stop signal at position 163 of the GJB6 protein, written as p.Arg163Ter or p.R108*. The substitution is predicted to result in a non-functional GJB6 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH), but it has been described in 2 alleles out of 121114, in the ExAC database, all of them belonging to heterozygous carries of European origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117485 | SCV003801030 | uncertain significance | not specified | 2023-01-31 | criteria provided, single submitter | clinical testing | Variant summary: GJB6 c.322C>T (p.Arg108X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. Truncations downstream of this position have not been observed at our laboratory but at-least one has been reported in association with non-syndromic hearing loss in the HGMD database. The variant allele was found at a frequency of 1.2e-05 in 251238 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.322C>T in individuals affected with Hidrotic Ectodermal Dysplasia Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |