ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24314_24317dup (p.Leu8106fs) (rs781667543)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542569 SCV000640739 pathogenic Nemaline myopathy 2 2017-01-23 criteria provided, single submitter clinical testing This sequence change inserts 2 nucleotides in exon 172 of the NEB mRNA (c.24314_24317dup), causing a frameshift at codon 8106. This creates a premature translational stop signal (p.Leu8106Phefs*30) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported 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 RCV000588489 SCV000697817 likely pathogenic Nemaline myopathy 2017-03-20 criteria provided, single submitter clinical testing Variant summary: The NEB c.24314_24317dupTGTT (p.Leu8106Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent NEB protein due to nonsense mediated decay, which are known disease mechanisms in nemaline myopathy. This variant is absent in 34482 control chromosomes from ExAC. This variant is reported in one family with typical nemaline myopathy in compound heterozygous state with c.1172_1173del (p.Tyr391*) (Lehtokari_2014). No genotypic and phenotypic details of the family members are provided in the study. It was also found in three colorectal cancer samples without confirmation of somatic status in COSMIC database. Truncations downstream of this position have been classified as pathogenic by our laboratory and other labs in ClinVar (e.g. p.Arg8187X, c.24771delT, c.24632_24633delCT). Taken together, this variant is classified as likely pathogenic.
Counsyl RCV000542569 SCV001132441 likely pathogenic Nemaline myopathy 2 2017-05-23 no assertion criteria provided clinical testing

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