Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000538236 | SCV000650903 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-06-24 | 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: 471976). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs770337434, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 482 of the FLNC protein (p.Arg482Gln). |
| Ambry Genetics | RCV004024190 | SCV003539171 | uncertain significance | Cardiovascular phenotype | 2021-10-26 | criteria provided, single submitter | clinical testing | The c.1445G>A (p.R482Q) alteration is located in exon 9 (coding exon 9) of the FLNC gene. This alteration results from a G to A substitution at nucleotide position 1445, causing the arginine (R) at amino acid position 482 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV003231646 | SCV003930155 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; 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 |