Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000537008 | SCV000658918 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2019-03-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 205 of the GJB1 protein (p.Asn205Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with X-linked Charcot-Marie-Tooth disease (CMTX) in 2 families (PMID: 24327141, 10071100), and has also been reported in multiple unrelated individuals affected with CMTX (PMID: 9452099, 9401007, 12497641, 19259128, 27544631, 28469099). ClinVar contains an entry for this variant (Variation ID: 10442). While one experimental study did not detect a functional effect for this variant (PMID: 15006706), a second study found that it caused increased perinuclear localization compared to wildtype GJB1 protein (PMID: 12111842). For these reasons, this variant has been classified as Pathogenic. |
Athena Diagnostics Inc | RCV000991856 | SCV001143682 | pathogenic | not provided | 2019-08-15 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality (0/201577 chr). Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. The gain of a new splice site is predicted. Results on protein functions were conflicting. Moderate co-segregation with disease in affected individuals from a single family. |
Ce |
RCV000991856 | SCV001245767 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000011187 | SCV000031414 | pathogenic | Charcot-Marie-Tooth Neuropathy X Type 1 | 1999-02-01 | no assertion criteria provided | literature only | |
Gene |
RCV000011187 | SCV000040509 | pathologic | Charcot-Marie-Tooth Neuropathy X Type 1 | 2010-04-15 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |