Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000276668 | SCV000399422 | uncertain significance | Brittle cornea syndrome 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001850712 | SCV002175779 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with glutamine at codon 2906 of the ZNF469 protein (p.Leu2906Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ZNF469-related conditions. 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: "Probably 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, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV003298380 | SCV003999384 | uncertain significance | Cardiovascular phenotype | 2023-04-01 | criteria provided, single submitter | clinical testing | The p.L2906Q variant (also known as c.8717T>A), located in coding exon 2 of the ZNF469 gene, results from a T to A substitution at nucleotide position 8717. The leucine at codon 2906 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
Gene |
RCV001850712 | SCV005079215 | uncertain significance | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |