Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559484 | SCV000658914 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2017-04-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 172 of the GJB1 protein (p.Pro172Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with Charcot-Marie-Tooth disease, type X1 (CMTX1)(PMID: 9856562, 27098783, 21692908). It has also been reported to segregate with disease in a family affected with CMTX1 (PMID: 9633821). This variant is also known as c.577 C>T in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789937 | SCV000929322 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |