ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.515C>T (p.Pro172Leu)

dbSNP: rs1555937218
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559484 SCV000658914 pathogenic Charcot-Marie-Tooth Neuropathy X 2024-01-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 172 of the GJB1 protein (p.Pro172Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease, type X1 (CMTX1) (PMID: 9633821, 9856562, 21692908, 27098783). It has also been observed to segregate with disease in related individuals. This variant is also known as c.577 C>T. ClinVar contains an entry for this variant (Variation ID: 477599). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789937 SCV000929322 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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