Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV000208843 | SCV004017785 | pathogenic | Von Hippel-Lindau syndrome | 2023-04-06 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 22825683]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 22265326, 34036514, 19464396, 12202531, 8956040]. |
Invitae | RCV003765349 | SCV004569522 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 114 of the VHL protein (p.Gly114Arg). This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 7728151, 12202531, 19464396, 27527340). ClinVar contains an entry for this variant (Variation ID: 223193). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Genomic Diagnostic Laboratory, |
RCV000208843 | SCV000264717 | pathogenic | Von Hippel-Lindau syndrome | 2016-02-26 | no assertion criteria provided | clinical testing |