Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040086 | SCV001203641 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2022-10-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala40 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 12536289, 28768847), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GJB1 function (PMID: 12460545). 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 not expected to disrupt GJB1 protein function. ClinVar contains an entry for this variant (Variation ID: 637200). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 8800924, 28768847). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 40 of the GJB1 protein (p.Ala40Val). |
| Inherited Neuropathy Consortium | RCV000789265 | SCV000928618 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |