Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001241679 | SCV001414713 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1816 of the FLNC protein (p.Asp1816Asn). 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: 966895). 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. |
| Ambry Genetics | RCV002348823 | SCV002648106 | uncertain significance | Cardiovascular phenotype | 2022-06-02 | criteria provided, single submitter | clinical testing | The p.D1816N variant (also known as c.5446G>A), located in coding exon 33 of the FLNC gene, results from a G to A substitution at nucleotide position 5446. The aspartic acid at codon 1816 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. |
| Revvity Omics, |
RCV003145465 | SCV003833192 | uncertain significance | not provided | 2021-01-07 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003963146 | SCV004783820 | uncertain significance | FLNC-related disorder | 2023-11-30 | criteria provided, single submitter | clinical testing | The FLNC c.5446G>A variant is predicted to result in the amino acid substitution p.Asp1816Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |