Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002000484 | SCV002261614 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-04-23 | criteria provided, single submitter | clinical testing | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 973 of the FLNC protein (p.Gly973Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| New York Genome Center | RCV002227573 | SCV002506767 | uncertain significance | Primary dilated cardiomyopathy | 2021-05-21 | criteria provided, single submitter | clinical testing | The c.2917G>A (p.Gly973Ser) variant identified in the FLNC gene substitutes a very well conserved Glycine for Serine at amino acid 973/2726 (econ19/48). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.042) and Pathogenic (REVEL; score:0.8159) to the function of the canonical transcript. This variant is absent fromClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Gly973 residue is within the 8th Filamin repeat of theprotein (UniProtKB:Q14315). The c.2917G>A (p.Gly973Ser) variant identified in the FLNC gene is reported as a Variant of Uncertain Significance. |