Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001339003 | SCV001532715 | uncertain significance | Primary dilated cardiomyopathy | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 665 of the NEBL protein (p.Thr665Pro). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 1036051). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. |
Ambry Genetics | RCV004827808 | SCV005457506 | uncertain significance | not specified | 2024-07-30 | criteria provided, single submitter | clinical testing | The p.T665P variant (also known as c.1993A>C), located in coding exon 20 of the NEBL gene, results from an A to C substitution at nucleotide position 1993. The threonine at codon 665 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |