Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000538826 | SCV000646240 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2023-08-16 | criteria provided, single submitter | clinical testing | 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. 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: 469037). This variant has not been reported in the literature in individuals affected with TRPV4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 510 of the TRPV4 protein (p.Arg510Trp). |
| Ambry Genetics | RCV002395418 | SCV002708234 | uncertain significance | Inborn genetic diseases | 2022-08-01 | criteria provided, single submitter | clinical testing | The p.R510W variant (also known as c.1528C>T), located in coding exon 8 of the TRPV4 gene, results from a C to T substitution at nucleotide position 1528. The arginine at codon 510 is replaced by tryptophan, 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. |