Submissions for variant NM_001271208.2(NEB):c.9181A>T (p.Met3061Leu) (rs143473183)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523543	SCV000618640	uncertain significance	not specified	2017-06-30	criteria provided, single submitter	clinical testing	Another variant of uncertain significance has been identified in the NEB gene. The M3061L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M3061L variant is observed in 45/9802 (0.5%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M3061L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000712397	SCV000763130	likely benign	not provided	2019-02-27	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000712397	SCV000842878	uncertain significance	not provided	2018-07-20	criteria provided, single submitter	clinical testing