Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001309128 | SCV001498616 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-07-17 | criteria provided, single submitter | clinical testing | 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: 1011345). 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. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1506 of the FLNC protein (p.Thr1506Ser). |
| Ambry Genetics | RCV002341620 | SCV002639045 | uncertain significance | Cardiovascular phenotype | 2021-06-21 | criteria provided, single submitter | clinical testing | The p.T1506S variant (also known as c.4517C>G), located in coding exon 26 of the FLNC gene, results from a C to G substitution at nucleotide position 4517. The threonine at codon 1506 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available 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. |
| Gene |
RCV003314684 | SCV004014526 | uncertain significance | not provided | 2023-01-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |