Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000687393 | SCV000814957 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2019-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with methionine at codon 505 of the TRPV4 protein (p.Thr505Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs375574238, ExAC 0.02%). 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: "Probably Damaging"; 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. |