ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.479G>A (p.Arg160Gln) (rs139300843)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235717 SCV000292700 uncertain significance not provided 2015-09-02 criteria provided, single submitter clinical testing The R160Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R160Q variant was not observed with any significant frequency in approximately 6,500 individuals of European and ancestry in the NHLBI Exome Sequencing Project. The R160Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations have not been reported in nearby residues in the Human Gene Mutation Database in association with neuropathy (Stenson et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000537457 SCV000646251 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 160 of the TRPV4 protein (p.Arg160Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs139300843, ExAC 0.003%). This variant has not been reported in the literature in individuals with a TRPV4-related disease. ClinVar contains an entry for this variant (Variation ID: 245674). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on TRPV4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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