Submissions for variant NM_006393.3(NEBL):c.383A>T (p.Gln128Leu)

dbSNP: rs139809958

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000215497	SCV000272205	uncertain significance	not specified	2015-03-11	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gln128Leu var iant in NEBL has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.2% (19/10400) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs139809958 ). Computational prediction tools and conservation analysis do not provide stron g support for or against an impact to the protein. In summary, while the clinica l significance of the p.Gln128Leu variant is uncertain, its frequency suggests t hat it is more likely to be benign.
GeneDx	RCV000767180	SCV000536383	uncertain significance	not provided	2018-11-13	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NEBL gene. The Q128L variant has not been published as pathogenic or been reported as benign to our knowledge. The Q128L 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. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (Q128R) has been reported in association with DCM and endocardial fibroelastosis in a newborn (Purevjav et al., 2010); however the pathogenicity of this variant has not been definitively determined. Nevertheless, this variant has been observed in approximately 0.2% of alleles from individual of African ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server; Exome Aggregation Consortium).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087987	SCV001004364	likely benign	Primary dilated cardiomyopathy	2023-12-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000215497	SCV005457538	uncertain significance	not specified	2024-12-04	criteria provided, single submitter	clinical testing	The c.383A>T (p.Q128L) alteration is located in exon 5 (coding exon 5) of the NEBL gene. This alteration results from a A to T substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.