ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.649G>A (p.Ala217Thr) (rs187864727)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464061 SCV000549250 uncertain significance Charcot-Marie-Tooth disease type 2C 2016-09-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 217 of the TRPV4 protein (p.Ala217Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases at a very low frequency (rs187864727, 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on 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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