ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.187G>A (p.Val63Ile)

dbSNP: rs116840818
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217618 SCV000278980 pathogenic not provided 2023-03-27 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 10093067, 30569560, 15006706, 20301548, 9099841, 12477701, 9633821, 12542510, 11393532, 17100997, 9364054, 25025039, 8162049, 9361298, 32376792)
Athena Diagnostics RCV000217618 SCV000613479 pathogenic not provided 2016-03-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001064548 SCV001229458 pathogenic Charcot-Marie-Tooth Neuropathy X 2023-12-20 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 63 of the GJB1 protein (p.Val63Ile). 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: 8162049, 10093067, 12542510). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21081). 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) has been performed at Invitae 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: 9364054, 11393532, 15006706). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000217618 SCV001245762 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing
GeneReviews RCV000020171 SCV000040500 not provided Charcot-Marie-Tooth disease X-linked dominant 1 no assertion provided literature only
Inherited Neuropathy Consortium RCV000789665 SCV000929039 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Natera, Inc. RCV000789665 SCV001462643 pathogenic Charcot-Marie-Tooth disease 2020-09-16 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000217618 SCV001924182 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000217618 SCV001955069 pathogenic not provided no assertion criteria provided clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami RCV000020171 SCV004174730 uncertain significance Charcot-Marie-Tooth disease X-linked dominant 1 2016-01-06 no assertion criteria provided literature only

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