Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Program, |
RCV001253785 | SCV001427089 | likely pathogenic | FLNC-associated cardiomyopathy | 2019-10-16 | no assertion criteria provided | clinical testing | The p.Arg1762Profs*21 variant in the FLNC gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Arg1762Profs*21 variant results in a 1 bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 21 amino acids downstream. Heterozygous loss of function is an established mechanism of disease for the FLNC gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Arg1762Profs*21 variant as likely pathogenic for FLNC-associated cardiomyopathy in an autosomal dominant manner based on the information above. [ACMG evidence codes used: PVS1; PM2] |