ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.392T>C (p.Leu131Pro) (rs1555937166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698825 SCV000827513 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2020-01-09 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 131 of the GJB1 protein (p.Leu131Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. 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: 9818870, 12362307). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 576347). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Inherited Neuropathy Consortium RCV000789284 SCV000928637 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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