Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001906509 | SCV002173983 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2556 of the FLNC protein (p.Pro2556Ala). This variant is present in population databases (rs765967888, gnomAD 0.008%). 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: 1402606). 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 with a negative predictive value of 95%. 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. |
| Gene |
RCV002305633 | SCV002599562 | uncertain significance | not provided | 2022-05-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Revvity Omics, |
RCV002305633 | SCV004234803 | uncertain significance | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004042546 | SCV005017820 | uncertain significance | Cardiovascular phenotype | 2024-01-22 | criteria provided, single submitter | clinical testing | The p.P2556A variant (also known as c.7666C>G), located in coding exon 46 of the FLNC gene, results from a C to G substitution at nucleotide position 7666. The proline at codon 2556 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |