ClinVar Miner

Submissions for variant NM_001110219.3(GJB6):c.63del (p.Lys22fs) (rs770612890)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000354367 SCV000383104 uncertain significance GJB6-related disorders 2018-05-03 criteria provided, single submitter clinical testing The GJB6 c.63delG (p.Lys22ArgfsTer13) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.00070 in the African American population of the Exome Sequencing Project. Based on the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for GJB6-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Counsyl RCV000409500 SCV000487352 likely pathogenic Hidrotic ectodermal dysplasia syndrome 2016-07-22 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000440483 SCV000511699 likely pathogenic not provided 2017-02-10 criteria provided, single submitter clinical testing
Invitae RCV001221511 SCV001393560 uncertain significance Deafness, autosomal recessive 1A; Deafness, autosomal recessive 1b; Deafness, autosomal dominant 3b; Hidrotic ectodermal dysplasia syndrome 2019-07-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GJB6 gene (p.Lys22Argfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 240 amino acids of the GJB6 protein. This variant is present in population databases (rs770612890, ExAC 0.04%). This variant has been observed as a single heterozygous variant in individuals affected with profound, congenital non-syndromic hearing loss (PMID: 16547895). ClinVar contains an entry for this variant (Variation ID: 311382). This variant disrupts a region of the protein in which other variant(s) (p.Pro70Leu) have been observed in individuals with GJB6-related conditions (PMID: 28501645). This suggests that this may be a clinically significant region of the GJB6 protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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