Submissions for variant NM_001271208.2(NEB):c.4471G>A (p.Val1491Met) (rs7426114)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000081137	SCV000113045	benign	not specified	2013-04-05	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000081137	SCV000269431	benign	not specified	2014-11-26	criteria provided, single submitter	clinical testing	This is a RefSeq error. The reference base (c.4471G) is the minor allele. This a llele (G) has been identified in 17% (1414/8444) of European American chromosome s and 68% (2878/4234) of African American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs7426114) and thus meets criteria to be classified as benign.
PreventionGenetics,PreventionGenetics	RCV000081137	SCV000307357	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000348796	SCV000416999	benign	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 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.
GeneDx	RCV000081137	SCV000519514	benign	not specified	2016-01-05	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.
Integrated Genetics/Laboratory Corporation of America	RCV000589707	SCV000697832	benign	not provided	2017-02-27	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.4471G>A (p.Val1491Met) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPs&GO not working, MutationTaster not captured due to low p-value). This variant was found in 89152/120710 control chromosomes (34995 homozygotes) at a frequency of 0.7385635, which is approximately 209 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), evidence that this variant is a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000589707	SCV001144725	benign	not provided	2019-03-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory,University of Chicago	RCV000081137	SCV000152016	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.