Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001321563 | SCV001512399 | uncertain significance | Primary dilated cardiomyopathy | 2022-07-11 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1021748). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 377 of the NEBL protein (p.Glu377Gly). |
| Ambry Genetics | RCV004035037 | SCV004000573 | uncertain significance | not specified | 2023-05-07 | criteria provided, single submitter | clinical testing | The p.E377G variant (also known as c.1130A>G), located in coding exon 12 of the NEBL gene, results from an A to G substitution at nucleotide position 1130. The glutamic acid at codon 377 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |