Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001208068 | SCV001379440 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-08-03 | 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: 938780). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs779184516, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1150 of the FLNC protein (p.Arg1150Trp). |
Gene |
RCV001773466 | SCV002001783 | uncertain significance | not provided | 2020-01-28 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
Ambry Genetics | RCV002451446 | SCV002617154 | uncertain significance | Cardiovascular phenotype | 2024-02-29 | criteria provided, single submitter | clinical testing | The p.R1150W variant (also known as c.3448C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3448. The arginine at codon 1150 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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, |
RCV001773466 | SCV003831413 | uncertain significance | not provided | 2021-04-12 | criteria provided, single submitter | clinical testing |