Submissions for variant NM_170707.4(LMNA):c.29C>T (p.Thr10Ile)

dbSNP: rs57077886

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000057387	SCV000293391	likely pathogenic	not provided	2016-01-27	criteria provided, single submitter	clinical testing	A T10I variant that is likely pathogenic was identified in the LMNA gene. It has been reported in one patient with Seip syndrome (Csoka et al., 2004) and as a de novo variant in one patient with atypical lipodystrophy (Mory et al., 2008). The T10I variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T10I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. Functional studies show that a cell line with the T10I likely pathogenic variant from a patient with Seip syndrome had abnormal nuclei (Csoka et al., 2004). Garg et al. (2009) observed nuclear abnormalities in cells from patients with atypical Progeria syndrome who carried the T10I variant
Genetic Services Laboratory, University of Chicago	RCV000502816	SCV000595615	likely pathogenic	Familial partial lipodystrophy, Dunnigan type	2016-02-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000622546	SCV000741340	pathogenic	Inborn genetic diseases	2016-03-15	criteria provided, single submitter	clinical testing
OMIM	RCV000015599	SCV000035864	pathogenic	Dilated cardiomyopathy 1A	2003-08-01	no assertion criteria provided	literature only
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057387	SCV000088500	not provided	not provided		no assertion provided	not provided
Medical Research Institute, Tokyo Medical and Dental University	RCV000755005	SCV000809014	pathogenic	Lipodystrophy	2017-10-04	no assertion criteria provided	research	Patient, a 31 year-old woman, was noted to present with generalized lipodystrophy in childhood. She had hypertriglyceridemia. Metreleptin therapy was started. Aortic stenosis was noted and aortic valve implantation was conducted. This mutation was heterozygous.