Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523313 | SCV000618219 | uncertain significance | not provided | 2018-12-31 | criteria provided, single submitter | clinical testing | The R83H variant of uncertain significance in the PRDM5 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, this variant has also been identified in conjunction with additional cardiogenetic variants in individuals referred for connective tissue disorder genetic testing at GeneDx. So far, segregation data is absent for these individuals. The R83H variant is observed in 8/126550 (0.01%) alleles from individuals of European (Non-Finnish) ancestry in large population cohorts (Lek et al., 2016). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, R83H is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, although a missense variant in the same residue in the PRDM5 gene (R83C) has been reported in the Human Gene Mutation Database in association with brittle cornea syndrome (Stenson et al., 2014), the pathogenicity of this variant has not been definitively determined. |
| Labcorp Genetics |
RCV000523313 | SCV002189724 | uncertain significance | not provided | 2022-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 83 of the PRDM5 protein (p.Arg83His). This variant is present in population databases (rs201945549, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PRDM5-related conditions. ClinVar contains an entry for this variant (Variation ID: 449806). 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 disruptive. 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 | RCV002431481 | SCV002742830 | uncertain significance | Cardiovascular phenotype | 2024-10-28 | criteria provided, single submitter | clinical testing | The p.R83H variant (also known as c.248G>A), located in coding exon 3 of the PRDM5 gene, results from a G to A substitution at nucleotide position 248. The arginine at codon 83 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Fulgent Genetics, |
RCV002490906 | SCV002791769 | uncertain significance | Brittle cornea syndrome 2 | 2022-05-12 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000523313 | SCV005410599 | uncertain significance | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing |