Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048344 | SCV001212344 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2019-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 179 of the TRPV4 protein (p.Arg179Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs751647405, ExAC 0.04%). This variant has not been reported in the literature in individuals with TRPV4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
| ARUP Laboratories, |
RCV001286085 | SCV001472608 | uncertain significance | none provided | 2020-01-16 | criteria provided, single submitter | clinical testing | The TRPV4 c.535C>T; p.Arg179Cys variant (rs751647405), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in South Asian population with an allele frequency of 0.042% (13/30614 alleles) in the Genome Aggregation Database. The arginine at codon 179 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg179Cys variant is uncertain at this time. |