Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000552022 | SCV000658908 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2017-07-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 12 of the GJB1 protein (p.Gly12Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family affected with Charcot-Marie-Tooth disease, type X (PMID: 8266101). Experimental studies have shown that this missense change alters the structure of the GJB1 (also known as Cx32) protein such that a functional channel is not formed and the mutant protein is mislocalized to the Golgi apparatus instead of the plasma membrane (PMID: 9354338, 11325342, 15006706, 19638273, 9364054, 10646523, 22705201). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789811 | SCV000929195 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |