Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236009 | SCV000293451 | pathogenic | not provided | 2016-04-26 | criteria provided, single submitter | clinical testing | The R215W pathogenic variant has been reported previously in association with CMTX1(Fairweather et al., 1994; Dubourg et al., 2001) and functional studies show that R215W prevents theformation of functional channels (Omori et al., 1996; Castro et al., 1999). The R215W variant wasnot observed in approximately 6,500 individuals of European and African American ancestry,indicating that it is not a common benign variant in these populations. The R215W variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. In silico analysis predicts thisvariant is probably damaging to the protein structure/function. This substitution occurs at a positionwhere amino acids with properties similar to Arginine are tolerated across species and several missensevariants in nearby residues have been reported in the Inherited Peripheral Neuropathy (IPN) databaseand Human Gene Mutation Database in association with CMTX1 (Stenson et al., 2014). Therefore,the presence of the R215W pathogenic variant is consistent with a diagnosis of CMTX1 |
Athena Diagnostics Inc | RCV000236009 | SCV000613497 | pathogenic | not provided | 2016-11-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000688999 | SCV000816633 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2019-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 215 of the GJB1 protein (p.Arg215Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in many individuals and families affected with Charcot-Marie-Tooth disease, type 1X (CMT1X) (PMID: 8162049, 25947624, 11571214, 11835375, 27098783, 8698335, 9187667, 16912585, 22464564) and has been reported to segregate with CMT1X in an affected family (PMID: 8162049). This variant has also been reported in an affected individual with a CMT2 phenotype (PMID: 11437164). ClinVar contains an entry for this variant (Variation ID: 246098). Experimental studies have shown that this missense change adversely affects protein function in vitro (PMID: 8816997, 10234007). For these reasons, this variant has been classified as Pathogenic. |
Inherited Neuropathy Consortium | RCV000789850 | SCV000929235 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |