Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000690012 | SCV000817688 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1711 of the FLNC protein (p.Pro1711Leu). This variant is present in population databases (rs748879903, gnomAD 0.002%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30411535). ClinVar contains an entry for this variant (Variation ID: 569395). 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. |
| Blueprint Genetics | RCV000788521 | SCV000927669 | uncertain significance | not provided | 2018-05-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343452 | SCV002646601 | uncertain significance | Cardiovascular phenotype | 2024-02-13 | criteria provided, single submitter | clinical testing | The p.P1711L variant (also known as c.5132C>T), located in coding exon 30 of the FLNC gene, results from a C to T substitution at nucleotide position 5132. The proline at codon 1711 is replaced by leucine, an amino acid with similar properties. This variant was reported in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Cui H et al. Mol Genet Genomic Med, 2018 11;6:1104-1113). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002493170 | SCV002781492 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 | 2021-09-02 | criteria provided, single submitter | clinical testing |