Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000691175 | SCV000818921 | uncertain significance | Primary dilated cardiomyopathy | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 782 of the NEBL protein (p.Met782Val). This variant is present in population databases (rs200574474, gnomAD 0.05%). 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: 570332). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV004025078 | SCV003858020 | uncertain significance | not specified | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.M782V variant (also known as c.2344A>G), located in coding exon 23 of the NEBL gene, results from an A to G substitution at nucleotide position 2344. The methionine at codon 782 is replaced by valine, an amino acid with highly 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. |