ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.559A>G (p.Lys187Glu)

dbSNP: rs1555937244
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654848 SCV000776750 uncertain significance Charcot-Marie-Tooth Neuropathy X 2023-10-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 187 of the GJB1 protein (p.Lys187Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9361298). ClinVar contains an entry for this variant (Variation ID: 543925). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV002248849 SCV002517136 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV003482294 SCV004229562 likely pathogenic not provided 2023-03-07 criteria provided, single submitter clinical testing This variant has been identified in at least one individual with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure.
Inherited Neuropathy Consortium RCV000789818 SCV000929202 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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