ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1378C>T (p.Arg460Trp) (rs34227547)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230906 SCV000290592 likely benign Charcot-Marie-Tooth disease axonal type 2C 2019-12-20 criteria provided, single submitter clinical testing
GeneDx RCV000235250 SCV000293905 uncertain significance not provided 2017-05-24 criteria provided, single submitter clinical testing The R460W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the populations of the 1000 Genomes Project. The R460W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved, and Tryptophan has been observed at this position in evolution. Additionally, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with TRPV4-related disorders (Stenson et al., 2014). Based on the currently available information, it is unclear whether the R460W variant is a pathogenic variant or a rare benign variant.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173243 SCV001336325 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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