Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001052901 | SCV001217136 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln707*) 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 dilated cardiomyopathy (PMID: 30067491). ClinVar contains an entry for this variant (Variation ID: 849024). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV003318659 | SCV004022612 | pathogenic | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | Nonsense 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: 35699965, 32112656, 30067491) |
| Ambry Genetics | RCV004031663 | SCV005017772 | pathogenic | Cardiovascular phenotype | 2024-02-07 | criteria provided, single submitter | clinical testing | The p.Q707* pathogenic mutation (also known as c.2119C>T), located in coding exon 13 of the FLNC gene, results from a C to T substitution at nucleotide position 2119. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant has been detected in an individual with dilated cardiomyopathy (Begay RL et al. JACC Clin Electrophysiol, 2018 Apr;4:504-514). 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. |