Submissions for variant NM_170707.4(LMNA):c.1560G>A (p.Trp520Ter)

dbSNP: rs794728595

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182370	SCV000234700	pathogenic	not provided	2016-05-25	criteria provided, single submitter	clinical testing	The W520X variant in the LMNA gene has been previously reported in a 43-year-old woman who presented with DCM and cardiac conduction disorder, including left bundle branch block, atrioventricular block, and sinus bradycardia. No indications for a neuromuscular phenotype were obtained (Stallmeyer et al., 2012). W520X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LMNA gene have been reported in association with dilated cardiomyopathy. In summary, W520X in the LMNA gene is interpreted as a disease-causing variant
Ambry Genetics	RCV002399656	SCV002704962	pathogenic	Cardiovascular phenotype	2019-10-24	criteria provided, single submitter	clinical testing	The p.W520* pathogenic mutation (also known as c.1560G>A), located in coding exon 9 of the LMNA gene, results from a G to A substitution at nucleotide position 1560. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Stallmeyer B et al. Genet Test Mol Biomarkers, 2012 Jun;16:543-9). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.