ClinVar

Description

Variant summary: GJB1 c.572_580delCCGTCTTCA (p.Thr191_Phe193del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was absent in 180670 control chromosomes (gnomAD). c.572_580delCCGTCTTCA has been reported in the literature in individuals affected with Charcot-Marie-Tooth disease X-linked dominant 1 (Bone_1997, Panosyan_2017, Record_2023). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, other variants involved in the region (Thr191_Phe193), including missense mutations, duplications, deletions, and insertions, were found in patients affected with Charcot-Marie-Tooth disease X-linked dominant 1 in HGMD database, supporting this region is functional important in GJB1 protein. The following publications have been ascertained in the context of this evaluation (PMID: 9361298, 9888385, 28768847, 37284795, 17052905, 18379723). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.