Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760793 | SCV000890688 | likely pathogenic | not provided | 2021-11-23 | 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 (Lek et al., 2016); Reported in an individual with dilated cardiomyopathy (Verdonschot et. al, 2020); This variant is associated with the following publications: (PMID: 31589614, 32112656) |
Invitae | RCV000809449 | SCV000949600 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-04-19 | 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: 620418). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1657*) 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 | RCV003362932 | SCV004054505 | pathogenic | Cardiovascular phenotype | 2023-07-28 | criteria provided, single submitter | clinical testing | The p.R1657* pathogenic mutation (also known as c.4969C>T), located in coding exon 30 of the FLNC gene, results from a C to T substitution at nucleotide position 4969. This changes the amino acid from an arginine to a stop codon within coding exon 30. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689875 | SCV005185407 | pathogenic | Primary familial dilated cardiomyopathy | 2024-05-07 | criteria provided, single submitter | clinical testing | Variant summary: FLNC c.4969C>T (p.Arg1657X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249230 control chromosomes. To our knowledge, no occurrence of c.4969C>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 620418). Based on the evidence outlined above, the variant was classified as pathogenic. |