ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24407_24410dup (p.Leu8137fs) (rs1344099907)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781649 SCV000919861 pathogenic Nemaline myopathy 2017-12-26 criteria provided, single submitter clinical testing Variant summary: The NEB c.24407_24410dupTGTT (p.Leu8137PhefsX18) variant results in a premature termination codon, predicted to cause a truncated or absent NEB 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., p.Arg8187X and p.Pro8211fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/178594 control chromosomes at a frequency of 0.0000112, which does not exceed the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355). In the literature, the variant has been reported in several patients and families with nemaline myopathy as both a compound heterozygous and homozygous allele. Taken together, this variant is classified as pathogenic.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000790962 SCV000930217 likely pathogenic Nemaline myopathy 2 2019-04-27 criteria provided, single submitter clinical testing
Invitae RCV000790962 SCV001412131 pathogenic Nemaline myopathy 2 2019-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu8137Phefs*18) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with NEB-related conditions (PMID: 25205138, 26019235). This variant is also known as c.24209_24212dupTGTT (p.L8071fs) in the literature. ClinVar contains an entry for this variant (Variation ID: 633333). Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic.

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