Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000654836 | SCV000776738 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2017-09-03 | criteria provided, single submitter | clinical testing | 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. A different missense substitution at this codon (p.Cys60Phe) has been determined to be pathogenic (PMID: 8162049, 8816997, 9452099, 10093067). This suggests that the cysteine residue is critical for GJB1 protein function and that other missense substitutions at this position may also be pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported to segregate with X-linked Charcot-Marie-Tooth disease in a single family (PMID: 25043634). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 60 of the GJB1 protein (p.Cys60Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Inherited Neuropathy Consortium | RCV000789055 | SCV000928404 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
| Inherited Neuropathy Consortium Ii, |
RCV003447152 | SCV004174748 | uncertain significance | Charcot-Marie-Tooth disease X-linked dominant 1 | 2016-01-06 | no assertion criteria provided | literature only |