ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.23140C>T (p.Arg7714Ter)

dbSNP: rs1575714905
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000986832 SCV001135971 pathogenic Nemaline myopathy 2 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001526961 SCV001737735 likely pathogenic Nemaline myopathy 2021-06-11 criteria provided, single submitter clinical testing Variant summary: NEB c.23245C>T (p.Arg7749X) 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 (Example: p.Arg8187X, p.Leu8414X, p.Arg8481X). The variant was absent in 223630 control chromosomes (gnomAD). c.23245C>T has been reported in the literature in individuals (compound heterozygous and heterozygous) affected with Nemaline Myopathy 2 (Lehtokari_2006, MokLee_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, modified Gomori trichrome staining of the biopsied muscle from a patient who was compound heterozygous for the variant of interest showed characteristic nemaline bodies (Mok Lee_2017). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000986832 SCV002229338 pathogenic Nemaline myopathy 2 2024-01-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg7749*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Nemaline myopathy (PMID: 16917880, 29669168). This variant is also known as p.Arg6013*. ClinVar contains an entry for this variant (Variation ID: 801764). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003467544 SCV004192606 pathogenic Arthrogryposis multiplex congenita 6 2023-02-24 criteria provided, single submitter clinical testing

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