ClinVar Miner

Submissions for variant NM_006393.3(NEBL):c.14T>C (p.Val5Ala)

gnomAD frequency: 0.00019  dbSNP: rs145770601
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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 RCV000038686 SCV000062364 uncertain significance not specified 2012-08-22 criteria provided, single submitter clinical testing The Val5Ala variant in NEBL has been identified in 1/4406 African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS; dbSNP rs145770601), though this could represent a presym ptomatic individual. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, and PolyPhen2) suggest that the variant may not impact the protein, though this information is not predictive enough to rule out pathog enicity. Additional information is needed to fully assess the variant's clinical significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000544555 SCV000623464 uncertain significance Primary dilated cardiomyopathy 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 5 of the NEBL protein (p.Val5Ala). This variant is present in population databases (rs145770601, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 45481). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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