Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822200 | SCV000962991 | likely pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-07-03 | criteria provided, single submitter | clinical testing | 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: 664165). This missense change has been observed in individuals with clinical features of FLNC-related conditions (PMID: 31245841; Invitae). This variant is present in population databases (rs773481064, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1194 of the FLNC protein (p.Ser1194Leu). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002453895 | SCV002613306 | uncertain significance | Cardiovascular phenotype | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.S1194L variant (also known as c.3581C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3581. The serine at codon 1194 is replaced by leucine, an amino acid with dissimilar properties. This alteration was reported in a subject with hypertrophic cardiomyopathy (HCM) (Ader F et al. Med Sci (Paris), 2018 Nov;34 Hors série n°2:39-41; Ader F et al. Clin Genet, 2019 10;96:317-329). 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. |