ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.37G>A (p.Val13Met) (rs104894820)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808363 SCV000948470 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2020-02-04 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 13 of the GJB1 protein (p.Val13Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs104894820, ExAC 0.01%). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 22944031). ClinVar contains an entry for this variant (Variation ID: 637129). 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. This variant disrupts the p.Val13 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 7477983, 27544631), which suggests that this may be a clinically significant amino acid residue. 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 RCV000789172 SCV000928524 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV001027489 SCV001190064 likely benign not provided no assertion criteria provided provider interpretation

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