Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002036853 | SCV002318017 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2023-06-25 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ser542 amino acid residue in TRPV4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21115951). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 1525659). This variant has not been reported in the literature in individuals affected with TRPV4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 542 of the TRPV4 protein (p.Ser542Cys). |
| Ambry Genetics | RCV002398130 | SCV002704290 | uncertain significance | Inborn genetic diseases | 2020-05-13 | criteria provided, single submitter | clinical testing | The p.S542C variant (also known as c.1625C>G), located in coding exon 9 of the TRPV4 gene, results from a C to G substitution at nucleotide position 1625. The serine at codon 542 is replaced by cysteine, an amino acid with dissimilar 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. |
| Gene |
RCV003314720 | SCV004014064 | uncertain significance | not provided | 2023-01-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |