ClinVar Miner

Submissions for variant NM_213569.2(NEBL):c.357+71783C>A (rs150000482)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227650 SCV000289524 uncertain significance Primary dilated cardiomyopathy 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 72 of the NEBL protein (p.Pro72Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs150000482, ExAC 0.01%). This variant has not been reported in the literature in individuals with NEBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 240647). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000520453 SCV000620974 uncertain significance not specified 2017-09-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEBL gene. The P72T variant has not been published as pathogenic or been reported as benign to our knowledge. However, it has been observed in 16/126636 (0.01%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016). The P72T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this variant has not been observed in a significant number of affected individuals, and it lacks both segregation and functional studies which would further clarify its pathogenicity.

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