ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1858G>A (p.Val620Ile) (rs121912633)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545248 SCV000646246 pathogenic Charcot-Marie-Tooth disease type 2C 2017-08-09 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 620 of the TRPV4 protein (p.Val620Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs121912633, ExAC 0.002%). This variant has been reported to segregate with autosomal dominant brachyolmia in a single family (PMID: 18587396) and has been reported to be de novo in an individual affected with hereditary motor and sensory neuropathy 2 (PMID: 20460441). ClinVar contains an entry for this variant (Variation ID: 4993). Experimental studies have shown that this missense change results in constitutive activation of the TRPV4 channel (PMID: 18587396, 21573172, 20037588). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000728663 SCV000856265 pathogenic not provided 2017-09-01 criteria provided, single submitter clinical testing
OMIM RCV000005281 SCV000025459 pathogenic Brachyrachia (short spine dysplasia) 2008-08-01 no assertion criteria provided literature only
GeneReviews RCV000202535 SCV000148033 pathogenic Skeletal dysplasia; Neuromuscular Diseases 2014-04-02 no assertion criteria provided literature only
GeneReviews RCV000202464 SCV000148034 pathogenic Skeletal dysplasia 2014-04-02 no assertion criteria provided literature only

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