Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002453264 | SCV002740136 | uncertain significance | Cardiovascular phenotype | 2020-12-23 | criteria provided, single submitter | clinical testing | The p.L85R variant (also known as c.254T>G), located in coding exon 1 of the LMNA gene, results from a T to G substitution at nucleotide position 254. The leucine at codon 85 is replaced by arginine, an amino acid with dissimilar properties. This variant was reported to segregate with disease in a family with dilated cardiomyopathy (DCM) and arrhythmia (Fatkin D et al. N Engl J Med, 1999 Dec;341:1715-24). Overall, functional studies showed no significant differences in lamin A but suggested possible impact on lamin C; however, the clinical impact of these findings is uncertain (Raharjo WH et al. J Cell Sci, 2001 Dec;114:4447-57; Ostlund C et al. J Cell Sci, 2001 Dec;114:4435-45; Sylvius N et al. Exp Cell Res, 2008 Aug;314:2362-75; Zwerger M et al. Hum Mol Genet, 2013 Jun;22:2335-49). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| OMIM | RCV000015568 | SCV000035833 | pathogenic | Dilated cardiomyopathy 1A | 1999-12-02 | no assertion criteria provided | literature only | |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057381 | SCV000088494 | not provided | not provided | no assertion provided | not provided |