Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041344 | SCV000065037 | pathogenic | Primary dilated cardiomyopathy | 2020-02-11 | criteria provided, single submitter | clinical testing | The p.Lys117GlufsX10 variant has been previously reported in 1 Chinese family with DCM, AV block, and atrial fibrillation (Pan 2009). The variant segregated with disease in 12 affected individuals (including 5 obligate carriers; Pan 2009). It has also been reported in ClinVar (Variation ID 48061), but was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 117 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In vitro functional studies support that the p.Lys117GlufsX10 variant leads to reduced mRNA and protein levels (Pan 2009). Loss of function of the LMNA gene is an established disease mechanism in autosomal dominant DCM. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant DCM. ACMG/AMP criteria applied: PVS1, PP1_Strong, PM2, PS3_Supporting. |
| Invitae | RCV000703206 | SCV000832095 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2019-05-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys117Glufs*10) in the LMNA gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). This variant has been reported to segregate with LMNA-related disease in a family and has been reported in an individual affected with dilated cardiomyopathy (PMID: 19328042, 22464770). This variant is also known as 0348_349insG, K117fs in the literature. ClinVar contains an entry for this variant (Variation ID: 48061). This variant is not present in population databases (ExAC no frequency). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057392 | SCV000088505 | not provided | not provided | no assertion provided | not provided | ||
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000057392 | SCV000925147 | pathogenic | not provided | 2012-08-22 | no assertion criteria provided | provider interpretation |