Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000654846 | SCV000776748 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2017-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 220 of the GJB1 protein (p.Arg220Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth (CMT) disease, however in these individuals, a duplication of the PMP22 gene was also identified (PMID: 16401743). Experimental studies have shown that this missense change preserves normal sub-cellular protein localization (PMID: 12460545, 21280457,). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Inherited Neuropathy Consortium | RCV000789831 | SCV000929215 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |