Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000547143 | SCV000659720 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val1643Thrfs*26) in the FLNC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 478128). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002341490 | SCV002641152 | pathogenic | Cardiovascular phenotype | 2023-11-20 | criteria provided, single submitter | clinical testing | The c.4926_4927insACGTCACA pathogenic mutation, located in coding exon 28 of the FLNC gene, results from an insertion of 8 nucleotides at position 4926, causing a translational frameshift with a predicted alternate stop codon (p.V1643Tfs*26). This mutation was reported in a dilated cardiomyopathy (DCM) cohort with limited clinical details provided (Morales A et al. Circ: Genom Precis Med. 2020 04;13:e002480). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this variant is expected to be causative of FLNC-related dilated cardiomyopathy; however, its clinical significance for FLNC-related hypertrophy/restrictive cardiomyopathy and/or skeletal myopathy is unclear. |
| Gene |
RCV003324768 | SCV004030663 | likely pathogenic | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | Identified in patients with DCM and peripartum cardiomyopathy (Morales et al., 2020; Goli et al., 2021); Identified as a maternally-inherited variant in two siblings with severe, early-onset DCM who also have a paternally-inherited frameshift variant in the TTN gene (Cowan et al., 2020); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32160020, 35699965, 32603605, 33874732) |
| University of Washington Center for Mendelian Genomics, |
RCV001543364 | SCV001761922 | likely pathogenic | Primary dilated cardiomyopathy | no assertion criteria provided | research |