Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002050485 | SCV002318357 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-06-08 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs765622614, ExAC 0.009%). This sequence change replaces glycine with valine at codon 456 of the FLNC protein (p.Gly456Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant has not been reported in the literature in individuals with FLNC-related conditions. 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Gene |
RCV002469451 | SCV002765635 | uncertain significance | not provided | 2022-06-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |