ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.556C>T (p.Arg186Ter) (rs773622769)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693039 SCV000820893 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2018-07-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg186*) in the TRPV4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs773622769, ExAC 0.003%). This variant has not been reported in the literature in individuals with TRPV4-related disease. A missense substitution downstream of this truncation (p.Arg232Cys) has been determined to be pathogenic (PMID: 20460441, 21288981, 24789864, 26048687). This suggests that the arginine residue is critical for TRPV4 protein function and that deletion of this residue may also be pathogenic. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TRPV4 cause disease. 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.

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