ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.145C>A (p.Pro49Thr)

gnomAD frequency: 0.00001  dbSNP: rs546287338
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804111 SCV000944005 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2024-06-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 49 of the TRPV4 protein (p.Pro49Thr). This variant is present in population databases (rs546287338, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TRPV4-related conditions. ClinVar contains an entry for this variant (Variation ID: 649227). 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 not expected to disrupt TRPV4 protein function with a negative 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.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173492 SCV001336581 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
GeneDx RCV001545388 SCV001764712 likely benign not provided 2020-09-14 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001545388 SCV002541561 uncertain significance not provided 2021-06-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002388505 SCV002701933 uncertain significance Inborn genetic diseases 2020-03-16 criteria provided, single submitter clinical testing The p.P49T variant (also known as c.145C>A), located in coding exon 1 of the TRPV4 gene, results from a C to A substitution at nucleotide position 145. The proline at codon 49 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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