ClinVar Miner

Submissions for variant NM_001110219.3(GJB6):c.209C>T (p.Pro70Leu)

gnomAD frequency: 0.00004  dbSNP: rs727505123
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156580 SCV000206299 uncertain significance not specified 2014-05-23 criteria provided, single submitter clinical testing The Pro70Leu variant in GJB6 has not been previously reported in individuals wit h hearing loss and was absent from large population studies. Computational predi ction tools and conservation analyses suggest that the Pro70Leu variant may impa ct the protein, though this information is not predictive enough to determine pa thogenicity. In summary, the clinical significance of the Pro70Leu variant is u ncertain.
Illumina Laboratory Services, Illumina RCV000404790 SCV000383099 uncertain significance Hidrotic ectodermal dysplasia syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV001558004 SCV001779865 uncertain significance not provided 2023-03-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30622556, 28501645)
Preventiongenetics, part of Exact Sciences RCV003390852 SCV004120175 uncertain significance GJB6-related condition 2023-08-01 criteria provided, single submitter clinical testing The GJB6 c.209C>T variant is predicted to result in the amino acid substitution p.Pro70Leu. This variant was reported in the homozygous state in single individual with hearing loss from a consanguineous family (Alkowari. 2017. PubMed ID: 28501645) and in the heterozygous state without a second potentially causative variant in another individual with hearing loss Morgan. 2018. PubMed ID: 30622556). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-20797411-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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