Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825597 | SCV000966939 | likely pathogenic | Primary dilated cardiomyopathy | 2018-02-22 | criteria provided, single submitter | clinical testing | The p.Leu197ThrfsX2 variant in LMNA has not been previously reported in individu als with dilated cardiomyopathy (DCM) or other LMNA-associated diseases and was absent from large population studies, though the ability of these studies to acc urately detect indels may be limited. This variant is a deletion of 2 amino acid s at positions 197 and 198 and an insertion of a threonine and a premature stop codon at these positions. This alteration is then predicted to lead to a truncat ed or absent protein. Heterozygous loss of LMNA function is strongly associated with DCM with or without conduction system disease, and/or skeletal myopathy. In summary, although additional studies are required to fully establish its clinic al significance, the p.Leu197ThrfsX2 variant is likely pathogenic. ACMG/AMP Crit eria applied (Richards 2015): PVS1, PM2. |