ClinVar Miner

Submissions for variant NM_213569.2(NEBL):c.358-10284A>G (rs770416802)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000420071 SCV000535029 uncertain significance not provided 2019-01-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEBL gene. The Q649R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q649R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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. However, to our knowledge no studies have been performed to determine the functional effect of the Q649R variant.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Invitae RCV000550794 SCV000623470 uncertain significance Primary dilated cardiomyopathy 2018-06-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 649 of the NEBL protein (p.Gln649Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs770416802, ExAC 0.003%). This variant has not been reported in the literature in individuals with NEBL-related disease. ClinVar contains an entry for this variant (Variation ID: 391870). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.