ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.241C>T (p.Leu81Phe)

dbSNP: rs876661143
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001869217 SCV002293778 pathogenic Charcot-Marie-Tooth Neuropathy X 2024-10-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 81 of the GJB1 protein (p.Leu81Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 10093067, 27804109; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 637207). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GJB1 protein function. Experimental studies have shown that this missense change affects GJB1 function (PMID: 27804109). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789273 SCV000928626 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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