ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24650_24651AG[2] (p.Arg8218fs) (rs755863625)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667317 SCV000791748 pathogenic Nemaline myopathy 2 2017-05-23 criteria provided, single submitter clinical testing
Invitae RCV000667317 SCV000949478 pathogenic Nemaline myopathy 2 2019-01-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg8218Serfs*9) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs755863625, ExAC 0.009%). This variant has been observed in combination with another NEB variant in individuals affected with nemaline myopathy (PMID: 25205138). ClinVar contains an entry for this variant (Variation ID: 552108). 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 RCV001194217 SCV001363576 likely pathogenic Nemaline myopathy 2019-07-29 criteria provided, single submitter clinical testing Variant summary: NEB c.24654_24655delAG (p.Arg8218SerfsX9) 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 (e.g. c.25241T>G, p.Leu8414X). The variant allele was found at a frequency of 1.2e-05 in 240344 control chromosomes (gnomAD). c.24654_24655delAG has been reported in the literature in individuals affected with Nemaline Myopathy (Lehtokari_2014). 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. A ClinVar submitter (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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