ClinVar Miner

Submissions for variant NM_006393.3(NEBL):c.2329C>T (p.Gln777Ter)

gnomAD frequency: 0.00002  dbSNP: rs752922937
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000217945 SCV000272200 uncertain significance not specified 2015-03-12 criteria provided, single submitter clinical testing The p.Gln777X variant in NEBL has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 1/66608 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). This nons ense variant leads to a premature termination codon at position 777, which is pr edicted to lead to a truncated or absent protein. Missense variants in NEBL have been reported in individuals with DCM and endocardial fibroelastosis (Purevjav 2010); however, the impact of loss of function variants in this gene has not bee n fully elucidated. In summary, the clinical significance of the p.Gln777X varia nt is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV002519644 SCV002999730 uncertain significance Primary dilated cardiomyopathy 2022-03-05 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 229044). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln777*) in the NEBL gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NEBL cause disease.

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