Submissions for variant NM_001271208.2(NEB):c.23582A>G (p.Asn7861Ser) (rs143602832)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520080	SCV000618641	uncertain significance	not specified	2017-06-30	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NEB gene. The N7861S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N7861S variant is observed in 47/9758 (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 N7861S 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 Asparagine 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	RCV000641479	SCV000763120	likely benign	Nemaline myopathy 2	2019-12-31	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000641479	SCV001292509	uncertain significance	Nemaline myopathy 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Natera, Inc.	RCV000641479	SCV001456463	uncertain significance	Nemaline myopathy 2	2019-11-11	no assertion criteria provided	clinical testing