ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.542T>C (p.Val181Ala) (rs876661252)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001350409 SCV001544808 uncertain significance Charcot-Marie-Tooth Neuropathy X 2020-05-15 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 181 of the GJB1 protein (p.Val181Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. 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: 14627639). ClinVar contains an entry for this variant (Variation ID: 637559). This variant has been reported to affect GJB1 protein function (PMID: 14627639). This variant disrupts the p.Val181 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9361298, 17100997, 19259128, 21692908, 25947624). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Inherited Neuropathy Consortium RCV000789797 SCV000929181 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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