Submissions for variant NM_021625.4(TRPV4):c.2440G>T (p.Val814Leu) (rs202075458)

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Total submissions: 1

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000470857	SCV000549251	uncertain significance	Charcot-Marie-Tooth disease axonal type 2C	2016-04-26	criteria provided, single submitter	clinical testing	This sequence change replaces valine with leucine at codon 814 of the TRPV4 protein (p.Val814Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs202075458, ExAC 0.001%) and has been observed in a reportedly unaffected individual at Invitae (Invitae database). The variant 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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