Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000248263 | SCV000320081 | pathogenic | Cardiovascular phenotype | 2016-02-16 | criteria provided, single submitter | clinical testing | The c.1157G>C pathogenic mutation (also known as p.R386T), located in coding exon 6 of the LMNA gene, results from a G to C substitution at nucleotide position 1157. This change occurs in the last base pair of coding exon 6, which makes it likely to have some effect on normal mRNA splicing. In addition to potential splicing impact, this alteration changes the arginine at codon 386 to threonine, an amino acid with some similar properties. This alteration has been reported in association with an unspecified cardiac phenotype and familial partial lipodystrophy (FPLD) and is located in the emerin binding domain (Carboni N et al. Acta Myol. 2013;32(1):7-17). Other alterations at the same nucleotide position, c.1157G>A (p.R386K) and c.1157G>T (p.R386M), have been reported in association with Emery-Dreifuss muscular dystrophy (EDMD) (Bonne G et al. Ann Neurol. 2000;48(2):170-80; Lassuthova P et al. Pediatr Neurol. 2009;41(2):127-30; Luo YB et al. J Med Genet. 2014;51(4):215-23). Based on segregation analysis in one family tested by our laboratory, this alteration was determined to be de novo in a proband with dilated cardiomyopathy. Based on the supporting evidence, c.1157G>A is interpreted as a disease-causing mutation. |