ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.834G>T (p.Glu278Asp)

dbSNP: rs529115496
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806161 SCV000946145 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2018-10-23 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Glu278 amino acid residue in TRPV4. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 20577006, 22419508, 22702953), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TRPV4-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 278 of the TRPV4 protein (p.Glu278Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid.

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