Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001576334 | SCV001803497 | uncertain significance | not provided | 2021-05-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Ambry Genetics | RCV002388609 | SCV002702474 | uncertain significance | Cardiovascular phenotype | 2021-09-20 | criteria provided, single submitter | clinical testing | The p.G503V variant (also known as c.1508G>T), located in coding exon 9 of the FLNC gene, results from a G to T substitution at nucleotide position 1508. The glycine at codon 503 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003771752 | SCV004569266 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 503 of the FLNC protein (p.Gly503Val). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. ClinVar contains an entry for this variant (Variation ID: 1208132). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (gnomAD no frequency). |