Submissions for variant NM_001164508.2(NEB):c.5102T>C (p.Val1701Ala)

gnomAD frequency: 0.00348  dbSNP: rs117271684

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000117760	SCV000230591	benign	not specified	2015-02-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000117760	SCV000307359	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001082597	SCV000416994	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.
GeneDx	RCV000117760	SCV000519883	benign	not specified	2016-05-18	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	RCV001082597	SCV000640810	benign	Nemaline myopathy 2	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586476	SCV000697833	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.5102T>C (p.Val1701Ala) variant involves the alteration of a conserved nucleotide and is predicted to be benign by 2/4 in silico tools (SNPs&GO not captured due to low reliability index). This variant was found in 962/107782 control chromosomes (24 homozygotes) from ExAC, predominantly observed in the East Asian subpopulation at a frequency of 0.081239 (640/7878). This frequency is about 23 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000586476	SCV000842874	benign	not provided	2018-03-26	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000117760	SCV000152017	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.
Natera, Inc.	RCV001082597	SCV001453497	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing