Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645547 | SCV000767296 | likely pathogenic | Charcot-Marie-Tooth disease type 2C | 2017-09-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 237 of the TRPV4 protein (p.Arg237Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease type 2C (CMT2C) in a single family (PMID: 27066566). Experimental studies have shown that this missense change disrupts protein function in vitro (PMID: 27066566). This missense change is located in a region of the TRPV4 protein where a significant number of previously reported TRPV4 missense mutations are found (PMID: 27066566). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. 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. |