ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.2042G>A (p.Gly681Asp)

gnomAD frequency: 0.00001  dbSNP: rs766420746
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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 RCV001172896 SCV001335971 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001873603 SCV002116947 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2024-07-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 681 of the TRPV4 protein (p.Gly681Asp). This variant is present in population databases (rs766420746, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 916861). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TRPV4 protein function. 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.
Ambry Genetics RCV002418603 SCV002719810 uncertain significance Inborn genetic diseases 2019-10-15 criteria provided, single submitter clinical testing The p.G681D variant (also known as c.2042G>A), located in coding exon 12 of the TRPV4 gene, results from a G to A substitution at nucleotide position 2042. The glycine at codon 681 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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