ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1337G>A (p.Arg446His) (rs143502097)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000645550 SCV000767299 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2019-09-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 446 of the TRPV4 protein (p.Arg446His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs143502097, ExAC 0.003%). This variant has not been reported in the literature in individuals with TRPV4-related disease. ClinVar contains an entry for this variant (Variation ID: 536865). 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173249 SCV001336332 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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