Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000168011 | SCV000218662 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2014-10-07 | criteria provided, single submitter | clinical testing | Because this sequence change is absent from the general population, has been observed in four independent CMT case reports, and disrupts the function of the GJB1 gene product, it has been classified as Pathogenic. This sequence change causes mislocalization of the protein product in the cells. Functional studies showed that the wild type protein is targeted to the cell membrane whereas the mutant protein is localized to the endoplasmic reticulum and therefore interferes with the formation of gap junctions (PMID: 12111842). This sequence change has been reported in patients and families affected with CMT (PMID:  9888385, 12457340, 10400511, 10521546) and is not present in population databases. This sequence change replaces alanine with valine at codon 39 of the GJB1 protein (p.Ala39Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. |
Inherited Neuropathy Consortium | RCV000789271 | SCV000928624 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |