Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000805229 | SCV000945177 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2018-10-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 278 of the TRPV4 protein (p.Glu278Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with spondylometaphyseal dysplasia and skeletal dysplasia with peripheral neuropathy (PMID: 20577006, 22419508). ClinVar contains an entry for this variant (Variation ID: 18434). Experimental studies have shown that this missense change contributes to constitutive TRPV4 activity by increased ATP binding (PMID: 22702953). 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. |
OMIM | RCV000005302 | SCV000025480 | pathogenic | Spondylometaphyseal dysplasia, Kozlowski type | 2010-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000202563 | SCV000148062 | pathogenic | Skeletal dysplasia; Neuromuscular disease | 2014-04-02 | no assertion criteria provided | literature only |