ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.1412_1414del (p.Phe471del)

dbSNP: rs515726154
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756825 SCV000884748 likely pathogenic not provided 2018-04-12 criteria provided, single submitter clinical testing The TRPV4 c.1412_1414delTCT; p.Phe471del variant (rs515726154, ClinVar variant ID 126464) has been detected in at least two cases of metatropic dysplasia, one of which was infantile lethal (Camacho 2010, Dai 2010). Functional studies in Xenopus oocytes demonstrated that the p.Phe471del variant, like other established pathogenic TRPV4 variants, results in a phenotype consistent with a constitutively open calcium channel compared to wild-type, and similar gain-of-function mutations have been associated with disease in other TRP channel proteins (Loukin 2011). This variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Based on the available information, the p.Phe471del variant is likely to be a pathogenic variant associated with metatropic dysplasia.
Genomic Medicine Lab, University of California San Francisco RCV001376047 SCV001573062 pathogenic Skeletal dysplasia and progressive central nervous system degeneration, lethal 2020-03-19 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000756825 SCV001961374 pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing TRPV4: PS2, PM2, PS4:Moderate, PM4:Supporting, PS3:Supporting
Labcorp Genetics (formerly Invitae), Labcorp RCV003505097 SCV004296213 likely pathogenic Charcot-Marie-Tooth disease axonal type 2C 2023-06-03 criteria provided, single submitter clinical testing This variant has been observed in individuals with clinical features of metatropic dysplasia (PMID: 20425821, 20577006, 22791502). This variant is not present in population databases (gnomAD no frequency). This variant, c.1412_1414del, results in the deletion of 1 amino acid(s) of the TRPV4 protein (p.Phe471del), but otherwise preserves the integrity of the reading frame. ClinVar contains an entry for this variant (Variation ID: 126464). 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. Experimental studies have shown that this variant affects TRPV4 function (PMID: 21573172). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant.
OMIM RCV002279715 SCV000025479 pathogenic Metatropic dysplasia 2010-10-01 no assertion criteria provided literature only
GeneReviews RCV000202564 SCV000148019 not provided Skeletal dysplasia no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.