Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001583266 | SCV001810928 | uncertain significance | not provided | 2021-11-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Labcorp Genetics |
RCV001583266 | SCV002162884 | uncertain significance | not provided | 2022-02-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1043 of the ZNF469 protein (p.Gly1043Val). This variant is present in population databases (no rsID available, gnomAD 0.005%). 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: 1211457). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Prevention |
RCV003394153 | SCV004120753 | uncertain significance | ZNF469-related disorder | 2023-02-27 | criteria provided, single submitter | clinical testing | The ZNF469 c.3128G>T variant is predicted to result in the amino acid substitution p.Gly1043Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0057% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-88497006-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV004995954 | SCV005544244 | likely benign | Cardiovascular phenotype | 2024-11-18 | 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. |