Submissions for variant NM_001164508.2(NEB):c.10809G>C (p.Trp3603Cys)

gnomAD frequency: 0.26237  dbSNP: rs10172023

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081108	SCV000113016	benign	not specified	2014-05-07	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000081108	SCV000269408	benign	not specified	2014-11-26	criteria provided, single submitter	clinical testing	p.Trp3603Cys in exon 73 of NEB: This variant is not expected to have clinical si gnificance because it has been identified in 33% (2784/8400) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs10172023).
PreventionGenetics, part of Exact Sciences	RCV000081108	SCV000307190	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000986839	SCV000416940	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	RCV000081108	SCV000519520	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588815	SCV000697800	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.10809G>C (p.Trp3603Cys) variant involves the alteration of a non-conserved nucleotide and 3/3 in silico tools (SNPsandGo and Mutation Taster not captured here due to low reliability index and p-value, respectively) predict a damaging outcome. This variant was found in 34849/120540 control chromosomes (5272 homozygotes) at a frequency of 0.2891074, which is approximately 82 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Therefore, the variant of interest has been classified as Benign.
Mendelics	RCV000986839	SCV001135978	benign	Nemaline myopathy 2	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000986839	SCV001722611	benign	Nemaline myopathy 2	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543078	SCV001761577	benign	Arthrogryposis multiplex congenita 6	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000986839	SCV001761578	benign	Nemaline myopathy 2	2021-07-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588815	SCV005238890	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000081108	SCV000151968	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.	RCV000986839	SCV001459408	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000081108	SCV001744068	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081108	SCV001951364	benign	not specified		no assertion criteria provided	clinical testing