Submissions for variant NM_001164508.2(NEB):c.22831C>T (p.Arg7611Ter)

gnomAD frequency: 0.00001  dbSNP: rs555582398

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175588	SCV001339225	pathogenic	Nemaline myopathy	2020-03-30	criteria provided, single submitter	clinical testing	Variant summary: NEB c.22936C>T (p.Arg7646X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. At least one publication reports experimental evidence that this variant affects mRNA splicing (Xiong_2015). The variant allele was found at a frequency of 1.2e-05 in 247810 control chromosomes. c.22936C>T has been reported in the literature in individuals affected with Nemaline Myopathy (example, Piga_2016, Lehtokari_2014). These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001222350	SCV001394445	pathogenic	Nemaline myopathy 2	2023-11-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg7646*) in the NEB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). This variant is present in population databases (rs555582398, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with nemaline myopathy (PMID: 16917880, 25205138). This variant is also known as g.216623C>T (p.Arg5910X). ClinVar contains an entry for this variant (Variation ID: 918157). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001580057	SCV003825973	pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV004570330	SCV005052108	pathogenic	Arthrogryposis multiplex congenita 6	2024-02-08	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580057	SCV001809517	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001580057	SCV001953927	pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001222350	SCV002084028	pathogenic	Nemaline myopathy 2	2021-02-10	no assertion criteria provided	clinical testing