Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002412394 | SCV002675784 | uncertain significance | Cardiovascular phenotype | 2022-04-09 | criteria provided, single submitter | clinical testing | The p.S2661N variant (also known as c.7982G>A), located in coding exon 47 of the FLNC gene, results from a G to A substitution at nucleotide position 7982. The serine at codon 2661 is replaced by asparagine, an amino acid with highly similar 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 | RCV003776464 | SCV004568746 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-01-17 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLNC protein function. ClinVar contains an entry for this variant (Variation ID: 1761473). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs781053612, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2661 of the FLNC protein (p.Ser2661Asn). |