Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001386350 | SCV001586541 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-04-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1073366). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gly1649Alafs*17) 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). |
| Ambry Genetics | RCV002341827 | SCV002642841 | pathogenic | Cardiovascular phenotype | 2023-07-14 | criteria provided, single submitter | clinical testing | The c.4946delG pathogenic mutation, located in coding exon 29 of the FLNC gene, results from a deletion of one nucleotide at nucleotide position 4946, causing a translational frameshift with a predicted alternate stop codon (p.G1649Afs*17). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. 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. |