Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649067 | SCV000770892 | pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 43 of the FLNC gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with dilated cardiomyopathy (PMID: 27908349, 28008423). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 539340). Studies have shown that disruption of this splice site results in skipping of exon 43 and introduces a premature termination codon (PMID: 28008423). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV003235326 | SCV003932679 | pathogenic | Hypertrophic cardiomyopathy 26 | 2023-06-16 | no assertion criteria provided | literature only |