ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.1858G>A (p.Val620Ile)

dbSNP: rs121912633
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000545248 SCV000646246 pathogenic Charcot-Marie-Tooth disease axonal type 2C 2024-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 620 of the TRPV4 protein (p.Val620Ile). This variant is present in population databases (rs121912633, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal dominant brachyolmia and hereditary motor and sensory neuropathy 2 (PMID: 18587396, 20460441). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4993). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TRPV4 protein function. Experimental studies have shown that this missense change affects TRPV4 function (PMID: 18587396, 20037588, 21573172). For these reasons, this variant has been classified as Pathogenic.
Eurofins Ntd Llc (ga) RCV000728663 SCV000856265 pathogenic not provided 2017-09-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre RCV001172890 SCV001335965 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV000728663 SCV001450405 pathogenic not provided 2018-11-19 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000728663 SCV001832462 pathogenic not provided 2019-11-30 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV003992145 SCV004812174 likely pathogenic Metatropic dysplasia 2023-01-02 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 not provided Skeletal dysplasia; Neuromuscular disease no assertion provided literature only
GeneReviews RCV000202464 SCV000148034 not provided Skeletal dysplasia no assertion provided literature only

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