ClinVar

Description

This sequence change deletes 9 nucleotides from exon 2 of the GJB1 mRNA (c.572_580delCCGTCTTCA). This leads to the deletion of 3 amino acid residues in the GJB1 protein (p.Thr191_Phe193del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two individuals affected with Charcot-Marie-Tooth disease (PMID: 9361298, 18379723). This variant is also known as c.573_581delCGTCTTCAT (p.Val192Met194del) in the literature. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant is located in a region of the GJB1 protein where a significant number of previously reported GJB1 missense mutations, deletions, and insertions are found (PMID: 11257785, 19691535, 15574129, 17052905, 9818870, 9361298, 10737979). These observations suggest that alterations within this region may affect protein function, but experiments have not been done to test this possibility. In summary, this variant is a rare deletion that has been observed in affected individuals and overlaps with previously reported Charcot-Marie-Tooth disease variants. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.