ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.22275C>G (p.Tyr7425Ter) (rs748922882)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701148 SCV000829932 pathogenic Nemaline myopathy 2 2018-03-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr7425*) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs748922882, ExAC 0.009%). This variant has been reported in several individuals affected with nemaline myopathy (PMID:12207938, 16917880). This variant is also known as p.Tyr5689* 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.
Integrated Genetics/Laboratory Corporation of America RCV000781648 SCV000919859 likely pathogenic Nemaline myopathy 2018-11-29 criteria provided, single submitter clinical testing Variant summary: NEB c.22275C>G (p.Tyr7425X) 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 (eg. c.24407_24410dupTGTT (p.Leu8137fsX18), c.24559C>T (p.Arg8187X), and c.24632_24633delCT (p.Pro8211fsX4)). The variant allele was found at a frequency of 8.1e-06 in 245950 control chromosomes (gnomAD). The variant, c.22275C>G, has been reported in the literature in an individual affected with Nemaline Myopathy 2 (Pelin_2002). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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