Submissions for variant NM_001271208.2(NEB):c.571G>C (p.Glu191Gln) (rs35686968)

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000117763	SCV000152020	uncertain significance	not provided	2013-08-23	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000250977	SCV000307367	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000250977	SCV000519544	benign	not specified	2016-05-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000552723	SCV000640823	benign	Nemaline myopathy 2	2020-12-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000250977	SCV000917877	benign	not specified	2018-08-06	criteria provided, single submitter	clinical testing	Variant summary: NEB c.571G>C (p.Glu191Gln) results in a conservative amino acid change located in the Nebulin repeat region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.016 in 276052 control chromosomes in the gnomAD database, including 81 homozygotes. The observed variant frequency is approximately 4.65 fold of the estimated maximal expected allele frequency for a pathogenic variant in NEB causing Nemaline Myopathy 2 phenotype (0.0035), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.571G>C in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cites variant as "benign." Based on the evidence outlined above, the variant was classified as benign.
Illumina Clinical Services Laboratory,Illumina	RCV000552723	SCV001295501	benign	Nemaline myopathy 2	2018-01-12	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics Inc	RCV000250977	SCV001476699	benign	not specified	2020-01-24	criteria provided, single submitter	clinical testing
Nilou-Genome Lab	RCV000552723	SCV001716399	benign	Nemaline myopathy 2	2021-05-18	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000552723	SCV001457275	benign	Nemaline myopathy 2	2020-06-08	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000117763	SCV001798916	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000250977	SCV001927085	benign	not specified		no assertion criteria provided	clinical testing