Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001040086 | SCV001203641 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2019-04-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 40 of the GJB1 protein (p.Ala40Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (PMID: 8800924, 28768847). This variant has been reported to affect GJB1 protein function (PMID: 12460545). 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. For these reasons, this variant has been classified as Pathogenic. |
Inherited Neuropathy Consortium | RCV000789265 | SCV000928618 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |