ClinVar Miner

Submissions for variant NM_006393.3(NEBL):c.2101C>A (p.Pro701Thr)

gnomAD frequency: 0.00016  dbSNP: rs371551337
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183638 SCV000236107 uncertain significance not provided 2014-10-08 criteria provided, single submitter clinical testing p.Pro701Thr (CCA>ACA): c.2101 C>A in exon 21 of the NEBL gene (NM_006393.2). The P701T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P701T variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P701T 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. This substitution occurs at a position that is class-conserved within mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Additionally, missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000704803 SCV000833770 uncertain significance Primary dilated cardiomyopathy 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 701 of the NEBL protein (p.Pro701Thr). This variant is present in population databases (rs371551337, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NEBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 201909). 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.
Ambry Genetics RCV004020231 SCV002724551 uncertain significance not specified 2024-10-12 criteria provided, single submitter clinical testing The c.2101C>A (p.P701T) alteration is located in exon 21 (coding exon 21) of the NEBL gene. This alteration results from a C to A substitution at nucleotide position 2101, causing the proline (P) at amino acid position 701 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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