Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000623486 | SCV000741175 | uncertain significance | Inborn genetic diseases | 2015-10-23 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected |
Invitae | RCV000645551 | SCV000767300 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2017-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 206 of the TRPV4 protein (p.Arg206Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200497189, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TRPV4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function 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. |