Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000803645 | SCV000943526 | uncertain significance | Primary dilated cardiomyopathy | 2022-07-26 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 648837). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. This variant is present in population databases (rs541364544, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 533 of the NEBL protein (p.Gly533Arg). |
| Ambry Genetics | RCV004028151 | SCV005025319 | uncertain significance | not specified | 2023-12-15 | criteria provided, single submitter | clinical testing | The p.G533R variant (also known as c.1597G>A), located in coding exon 16 of the NEBL gene, results from a G to A substitution at nucleotide position 1597. The glycine at codon 533 is replaced by arginine, an amino acid with dissimilar 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. |