ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.11627G>A (p.Trp3876Ter) (rs776569219)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521697 SCV000618662 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing The W3876X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although the W3876X has not been previously reported to our knowledge, a different nucleotide substitution resulting in the same nonsense variant has been reported in a family with nemaline myopathy who harbored an additional NEB variant (Lehtokari et al., 2014). Additionally, other downstream nonsense variants in the NEB gene have been previously reported in the Human Gene Mutation Database in association with nemaline myopathy (Stenson et al., 2014).
Invitae RCV000529040 SCV000640506 pathogenic Nemaline myopathy 2 2019-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp3876*) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776569219, ExAC 0.009%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 450119). The same truncation caused by a different nucleotide change (c.11628G>A) has been reported in the literature in an individual affected with nemaline myopathy (PMID: 25205138). Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000529040 SCV000798931 likely pathogenic Nemaline myopathy 2 2018-03-29 no assertion criteria provided clinical testing
Natera, Inc. RCV000529040 SCV001459400 pathogenic Nemaline myopathy 2 2020-09-16 no assertion criteria provided clinical testing

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