Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Phosphorus, |
RCV001823809 | SCV002073390 | uncertain significance | not specified | 2022-01-19 | criteria provided, single submitter | clinical testing | This missense variant results in an amino acid substitution of asparagine with lysine at codon 2532 of the FLNC gene (NM_001458.4). The variant has no entry in ClinVar and has not occurred in population databases. This position is not conserved. In silico functional algorithms agreed, with PolyPhen calling it benign, and SIFT tolerated, but no functional studies were performed to confirm these predictions. The variant has not occurred in literature associated with disease. Considering that this is a rare variant, whose impact on the protein and association with disease are unknown, it has been classified as a Variant of Uncertain Significance. |
Invitae | RCV001885365 | SCV002206638 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 2532 of the FLNC protein (p.Asn2532Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1339285). 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLNC protein function. 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. |
Ambry Genetics | RCV002388686 | SCV002674319 | uncertain significance | Cardiovascular phenotype | 2019-12-19 | criteria provided, single submitter | clinical testing | The p.N2532K variant (also known as c.7596T>A), located in coding exon 46 of the FLNC gene, results from a T to A substitution at nucleotide position 7596. The asparagine at codon 2532 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, lysine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |