ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.22936C>T (p.Arg7646Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV001222350 SCV001394445 pathogenic Nemaline myopathy 2 2019-10-18 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. This variant is present in population databases (rs555582398, ExAC 0.002%). This variant has been observed in individuals affected with nemaline myopathy (PMID: 16917880, 25205138). This variant is also known as g.216623C>T (p.Arg5910X) in the literature. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic.

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