Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001892181 | SCV002156673 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 469 of the PRDM5 protein (p.Ala469Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs757433292, ExAC 0.009%). This variant has not been reported in the literature in individuals with PRDM5-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Gene |
RCV001892181 | SCV002586554 | uncertain significance | not provided | 2022-10-06 | 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 |
| Ambry Genetics | RCV004041182 | SCV003708590 | uncertain significance | Cardiovascular phenotype | 2023-11-18 | criteria provided, single submitter | clinical testing | The p.A469V variant (also known as c.1406C>T), located in coding exon 12 of the PRDM5 gene, results from a C to T substitution at nucleotide position 1406. The alanine at codon 469 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |