Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649171 | SCV000770996 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro2513Glufs*12) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with arrhythmia (PMID: 30118858). ClinVar contains an entry for this variant (Variation ID: 539437). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004025773 | SCV005017804 | pathogenic | Cardiovascular phenotype | 2024-01-22 | criteria provided, single submitter | clinical testing | The c.7536_7548del13 pathogenic mutation, located in coding exon 45 of the FLNC gene, results from a deletion of 13 nucleotides at nucleotide positions 7536 to 7548, causing a translational frameshift with a predicted alternate stop codon (p.P2513Efs*12). 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 hypertrophic/restrictive cardiomyopathy and/or skeletal myopathy is unclear. |