Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000645557 | SCV000767307 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2019-07-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 448 of the TRPV4 protein (p.Glu448Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs373103155, ExAC 0.002%). 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. |