ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.1175G>A (p.Arg392Gln)

gnomAD frequency: 0.00004  dbSNP: rs770364304
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173250 SCV001336333 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
GeneDx RCV001565156 SCV001788446 uncertain significance not provided 2019-08-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32376792)
Invitae RCV003611548 SCV004561204 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 392 of the TRPV4 protein (p.Arg392Gln). This variant is present in population databases (rs770364304, gnomAD 0.003%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 916986). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TRPV4 protein function with a positive predictive value of 95%. 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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