Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000819239 | SCV000959888 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-05-22 | 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. 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: 661754). 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). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1232 of the FLNC protein (p.Gly1232Arg). |
| Ambry Genetics | RCV004029002 | SCV005017701 | uncertain significance | Cardiovascular phenotype | 2023-10-02 | criteria provided, single submitter | clinical testing | The p.G1232R variant (also known as c.3694G>A), located in coding exon 21 of the FLNC gene, results from a G to A substitution at nucleotide position 3694. The glycine at codon 1232 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Rajaie Cardiovascular, |
RCV002223137 | SCV002499631 | likely pathogenic | Hypertrophic cardiomyopathy 26 | no assertion criteria provided | research | The FLNC gene encodes Filamin C protein which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. In the study of Francesca Brun et al., 2020 (PMID: 31924696), they identified FLNC variants in two families with phenotypes of ARVC according to the 2010 task Force Criteria. The inheritance of this gene is autosomal dominant. |