Submissions for variant NM_007078.3(LDB3):c.1166_1167inv (p.Ala389Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183548	SCV000236017	uncertain significance	not provided	2014-03-26	criteria provided, single submitter	clinical testing	c.1166_1167delinsGG: p.Ala389Gly (A389G) in exon 8 of the LDB3 gene (NM_007078.2). The normal sequence with the bases that are deleted in braces and the brackets that are inserted in braces is: CCCG{CC}[GG]GCCC.To our knowledge, the c.1166_1167delCCinsGG (alternate HGVS nomenclature NM_007078.2:c.1166_1167invCC) or A389G variant has not been published as a mutation or as a benign polymorphism. The A389G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, the A389G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is relatively well conserved in mammals. In silico analysis predicts this variant is possibly damaging to the protein structure/function. However, no mutations in nearby residues have been reported in association with cardiomyopathy, suggesting this region of the protein may be tolerant to change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).