Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151550 | SCV000199685 | likely benign | not specified | 2014-04-04 | criteria provided, single submitter | clinical testing | Gly19Glu in exon 1 of NEBL: This variant is not expected to have clinical signif icance due to a lack of conservation across species, including mammals. Of note, >20 mammals and other species have a glutamine (Glu) at this position despite h igh nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. |
Invitae | RCV002514917 | SCV003250380 | uncertain significance | Primary dilated cardiomyopathy | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 19 of the NEBL protein (p.Gly19Glu). This variant is present in population databases (rs727503338, 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: 164772). 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 glutamic acid 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. |
Ambry Genetics | RCV000151550 | SCV004085420 | likely benign | not specified | 2023-07-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |