Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001042078 | SCV001205740 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-11-28 | 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: 840155). This missense change has been observed in individuals with hypertrophic cardiomyopathy and/or restrictive cardiomyopathy (PMID: 25351925, 30418145, 30919686). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2151 of the FLNC protein (p.Gly2151Ser). |
Gene |
RCV001557508 | SCV001779281 | likely pathogenic | not provided | 2022-11-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID#840155; ClinVar); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25351925, 28356264, 30919686) |
Human Genetics Bochum, |
RCV002508950 | SCV002818305 | likely pathogenic | Cardiomyopathy | 2022-11-25 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PP3_STR, PS4_MOD, PM2_SUP |
Illumina Laboratory Services, |
RCV001557508 | SCV003802858 | uncertain significance | not provided | 2022-11-18 | criteria provided, single submitter | clinical testing | The FLNC c.6451G>A (p.Gly2151Ser) missense variant results in the substitution of glycine at amino acid position 2151 with serine. The c.6451G>A variant has been reported in two unrelated indivduals with restrictive cardiomyopathy (PMID: 25351925; PMID 30919686). This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. The Gly2151 residue is located in the recurrent immunoglobulin domain. Based on the available evidence, the c.6451G>A (p.Gly2151Ser) variant is classified as a variant of uncertain significance for familial restrictive cardiomyopathy. |