Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516283 | SCV000613481 | pathogenic | not provided | 2016-12-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000552811 | SCV000658905 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2017-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 89 of the GJB1 protein (p.Leu89Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with CMTX1 (PMID: 26274329, 12457340, 9099841) and it has been reported to segregate with disease in a family affected with X-linked dominant Charcot-Marie-Tooth disease (CMTX1) (PMID: 17714866). This variant is also known as leu238pro in the literature. Experimental studies have found that this missense change impacts the cellular localization of the GJB1-encoded CX32 protein, preventing the formation of functional CX32 gap junctions (PMID: 27367520). For these reasons, this variant has been classified as Pathogenic. |
Inherited Neuropathy Consortium | RCV000789233 | SCV000928585 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |