Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001722446 | SCV000621018 | uncertain significance | not provided | 2019-10-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002376969 | SCV002687931 | uncertain significance | Cardiovascular phenotype | 2023-11-09 | criteria provided, single submitter | clinical testing | The p.R3078W variant (also known as c.9232C>T), located in coding exon 2 of the ZNF469 gene, results from a C to T substitution at nucleotide position 9232. The arginine at codon 3078 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |
| Fulgent Genetics, |
RCV002481728 | SCV002775556 | uncertain significance | Brittle cornea syndrome 1 | 2021-09-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001722446 | SCV003785999 | uncertain significance | not provided | 2022-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3078 of the ZNF469 protein (p.Arg3078Trp). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 452230). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |