Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000619007 | SCV000737304 | likely pathogenic | Cardiovascular phenotype | 2017-09-14 | criteria provided, single submitter | clinical testing | The c.1608+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 9 in the LMNA gene. This alteration has been reported in an individual with limb-girdle muscular dystrophy (LGMD1B) whose fibroblasts show blebbing of the nuclear envelope (Muchir A et al. Muscle Nerve. 2004;30:444-50). In addition, a disease-causing mutation at the same splice site, c.1608+5G>C, has been shown to impact splicing, causing retention of intron 9 and leading to a frameshift and premature truncation of the LMNA protein (Muchir A et al. Hum. Mol. Genet. 2000;9:1453-9). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, the c.1608+5G>A alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |