Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000994368 | SCV001147845 | uncertain significance | not provided | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004030174 | SCV002709347 | uncertain significance | not specified | 2024-04-12 | criteria provided, single submitter | clinical testing | The p.R547Q variant (also known as c.1640G>A), located in coding exon 16 of the NEBL gene, results from a G to A substitution at nucleotide position 1640. The arginine at codon 547 is replaced by glutamine, 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. |
Labcorp Genetics |
RCV003619732 | SCV004463572 | uncertain significance | Primary dilated cardiomyopathy | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 547 of the NEBL protein (p.Arg547Gln). This variant is present in population databases (rs747238199, gnomAD 0.0009%). 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: 806451). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |