ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.239A>G (p.Gln80Arg) (rs879254097)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235814 SCV000293448 likely pathogenic not provided 2021-08-20 criteria provided, single submitter clinical testing Functional studies show that the Q80R variant is capable of forming a functional gap junction protein, and the authors conclude that further functional studies are necessary to elucidate the effect, if any, of the Q80R variant (Wang et al., 2004); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30042657, 25449862, 15006706, 9361298, 28211240, 17353473, 8737658, 10873293, 10737979, 7580242)
Invitae RCV000466555 SCV000544779 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2016-07-18 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 80 of the GJB1 protein (p.Gln80Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in 5 individuals affected with X-linked Charcot-Marie-Tooth (CMT) disease (PMID: 7580242, 8737658, 17353473, 10737979. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that has been reported in several affected individuals, and is predicted to disrupt protein function. Functional studies demonstrating a mechanism for pathogenicity have not been published. For these reasons, this variant has been classified as likely Pathogenic.
Athena Diagnostics Inc RCV000235814 SCV000613480 pathogenic not provided 2016-12-22 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789226 SCV000928578 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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