Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020234 | SCV001181687 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-02 | criteria provided, single submitter | clinical testing | The c.341-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 2 of the VHL gene. This alteration was observed in a father and son, both with features of von Hippel-Lindau disease, and was shown to result in exon 2 skipping at levels higher than in controls (Gomy I et al. Fam. Cancer 2010 Dec;9:635-42). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site. Based on the available evidence, this alteration is classified as a pathogenic mutation. |
| Genetics and Molecular Pathology, |
RCV003447574 | SCV004175221 | pathogenic | Von Hippel-Lindau syndrome | 2023-04-28 | criteria provided, single submitter | clinical testing | The VHL c.341-1G>A variant is classified as Pathogenic (PVS1, PM2, PS4_moderate) The VHL c.341-1G>A variant is located at the canonical acceptor splice site of intron 1. Computational predictions support a deleterious effect on splicing and a likely disruption of the protein reading frame (PVS1). The variant has been reported in two unrelated individuals with a phenotype of VHL and RNA studies demonstrate skipping of exon 2 (PMID: 20567917, 11835384) (PS4_moderate) This variant is absent from population databases (PM2). The variant has been reported in dbSNP (rs1575927648) and in the HGMD database as disease causing (CS107609). It has been reported as pathogenic by another diagnostic laboratory (ClinVar Variation ID: 823743). |
| Baylor Genetics | RCV003467657 | SCV004208783 | pathogenic | Chuvash polycythemia | 2023-05-11 | criteria provided, single submitter | clinical testing |