Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000607758 | SCV000726277 | likely benign | not specified | 2018-01-05 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV001860321 | SCV002225880 | uncertain significance | not provided | 2022-07-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1460 of the ZNF469 protein (p.Pro1460Leu). This variant is present in population databases (rs565994438, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. ClinVar contains an entry for this variant (Variation ID: 514482). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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 | RCV004024976 | SCV005037671 | benign | Cardiovascular phenotype | 2023-10-05 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |