ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.832G>A (p.Glu278Lys) (rs267607148)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805229 SCV000945177 likely pathogenic Charcot-Marie-Tooth disease 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
GeneReviews RCV000202563 SCV000148062 pathogenic Skeletal dysplasia; Neuromuscular Diseases 2014-04-02 no assertion criteria provided literature only

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