Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000349637 | SCV000399283 | uncertain significance | Brittle cornea syndrome 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002411212 | SCV002722418 | uncertain significance | Cardiovascular phenotype | 2023-01-03 | criteria provided, single submitter | clinical testing | The p.P628T variant (also known as c.1882C>A), located in coding exon 1 of the ZNF469 gene, results from a C to A substitution at nucleotide position 1882. The proline at codon 628 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other 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, |
RCV000349637 | SCV002801419 | uncertain significance | Brittle cornea syndrome 1 | 2022-03-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002521070 | SCV003275380 | uncertain significance | not provided | 2022-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 628 of the ZNF469 protein (p.Pro628Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 320874). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 |
RCV003418009 | SCV004118502 | uncertain significance | ZNF469-related disorder | 2023-02-27 | criteria provided, single submitter | clinical testing | The ZNF469 c.1882C>A variant is predicted to result in the amino acid substitution p.Pro628Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-88495760-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |