Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003064736 | SCV003445253 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the GJB1 mRNA. The next in-frame methionine is located at codon 34. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with GJB1-related conditions (PMID: 20039784, 24627108, 24958582, 25614874, 25771809; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2138604). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects GJB1 function (PMID: 25771809). For these reasons, this variant has been classified as Pathogenic. |