Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000517827 | SCV000613491 | pathogenic | not provided | 2015-12-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000654852 | SCV000776754 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2019-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 183 of the GJB1 protein (p.Arg183His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with Charcot-Marie-Tooth disease, type X (PMID: 9187667, 27844031, 15719046, 27027447, 14960772, 28469099). Experimental studies have shown that this affects protein expression and function (PMID: 27844031, 12111842). A different missense substitution at this codon (p.Arg183Cys) has been determined to be pathogenic (PMID: 9187667, 11271367, 12111842). This suggests that the arginine residue is critical for GJB1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000517827 | SCV001245766 | pathogenic | not provided | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Inherited Neuropathy Consortium | RCV000789837 | SCV000929221 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |