Submissions for variant NM_170707.4(LMNA):c.3G>C (p.Met1Ile)

dbSNP: rs794728598

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236357	SCV000292999	pathogenic	not provided	2017-04-28	criteria provided, single submitter	clinical testing	The c.3 G>C pathogenic variant in the LMNA gene has not been reported as a disease-causing variant or as a benign polymorphism to our knowledge. This variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met. Two variants which affect the Met1 residue have been reported in association with laminopathies (Walter M et al., 2005; van Tintelen et al., 2007). Walter et al. (2005) identified a 15bp deletion starting at c.-3 that includes the Met1 codon in a family with symptoms of Emery-Driefuss muscular dystrophy, limb girdle muscular dystrophy with atrioventricular disturbance and dilated cardiomyopathy with conduction defects. van Tintelen et al. (2007) identified a deletion of the 5' end of the LMNA gene, including exon 1 and the Met1 codon in a family presenting with severe, early onset myocardial fibrosis. Also, a different nucleotide change at the same position, c.3 G>T, has been observed in other unrelated individuals tested for DCM at GeneDx. In summary, c.3 G>C in the LMNA gene is interpreted as a disease-causing variant"
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678713	SCV000804880	likely pathogenic	not specified	2015-10-16	no assertion criteria provided	clinical testing