ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.238C>A (p.Gln80Lys) (rs1602348981)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000792639 SCV000931947 pathogenic Charcot-Marie-Tooth Neuropathy X 2020-05-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 80 of the GJB1 protein (p.Gln80Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 22464564, Invitae). ClinVar contains an entry for this variant (Variation ID: 637563). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB1 protein function. This variant disrupts the p.Gln80 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7580242, 8737658, 10737979, 17353473). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789802 SCV000929186 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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