ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24559C>T (p.Arg8187Ter) (rs763364977)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000586673 SCV000697819 pathogenic Nemaline myopathy 2016-07-28 criteria provided, single submitter clinical testing Variant summary: The NEB c.24559C>T (p.Arg8187X) variant causes a nonsense mutation involving a conserved nucleotide resulting in a truncated NEB protein, a known mechanism for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals in the compound heterozygous state. Publications have indicated that the variant of interest could cause a intermediate phenotype. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763063 SCV000893561 pathogenic Nemaline myopathy 2 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000763063 SCV000915863 likely pathogenic Nemaline myopathy 2 2018-10-16 criteria provided, single submitter clinical testing The NEB c.18886C>T (p.Arg6296Ter) variant, also reported as c.24559C>T (p.Arg8187Ter), is a stop-gained variant predicted to result in a premature termination of the protein. The p.Arg8187Ter variant is reported in two studies, in which it is found in two patients in a compound heterozygous state with nemaline myopahty (Lehtokari et al. 2014; Piga et al. 2016). Control data are unavailable for this variant and it is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium or the Genome Aggregation Database in a region of good sequence coverage, thus the variant is presumed to be rare. Based on the evidence and potential impact of stop-gained variants, the p.Arg6296Ter variant is classified as likely pathogenic for autosomal recessive nemaline myopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000763063 SCV000953578 pathogenic Nemaline myopathy 2 2019-08-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg8187*) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with nemaline myopathy (PMID: 25205138, 27105866). ClinVar contains an entry for this variant (Variation ID: 496135). Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000763063 SCV001132439 pathogenic Nemaline myopathy 2 2016-11-18 no assertion criteria provided clinical testing

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