ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1781G>A (p.Arg594His) (rs77975504)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000498625 SCV000590827 pathogenic not provided 2016-05-27 criteria provided, single submitter clinical testing
Invitae RCV000691603 SCV000819389 pathogenic Charcot-Marie-Tooth disease type 2C 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 594 of the TRPV4 protein (p.Arg594His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in many individuals affected with spondylometaphyseal dysplasia, Kozlowski type (PMID: 19232556, 20577006, 21658220), as well as other related skeletal dysplasias (PMID: 20503319, 21658220). ClinVar contains an entry for this variant (Variation ID: 4994). Experimental studies have shown that this missense change increases basal calcium channel activity (PMID: 19232556, 21573172). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005282 SCV000025460 pathogenic Spondylometaphyseal dysplasia, Kozlowski type 2010-10-01 no assertion criteria provided literature only
OMIM RCV000005283 SCV000025461 pathogenic Parastremmatic dwarfism 2010-10-01 no assertion criteria provided literature only
GeneReviews RCV000202560 SCV000148025 pathogenic Skeletal dysplasia; Neuromuscular Diseases 2014-04-02 no assertion criteria provided literature only

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