ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1957A>G (p.Thr653Ala) (rs769927678)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475438 SCV000549249 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2017-01-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 653 of the TRPV4 protein (p.Thr653Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs769927678, ExAC 0.01%) but has not been reported in the literature in individuals with a TRPV4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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