Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000645550 | SCV000767299 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2C | 2019-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 446 of the TRPV4 protein (p.Arg446His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs143502097, ExAC 0.003%). This variant has not been reported in the literature in individuals with TRPV4-related disease. ClinVar contains an entry for this variant (Variation ID: 536865). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Molecular Genetics Laboratory, |
RCV001173249 | SCV001336332 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |