Submissions for variant NM_000551.4(VHL):c.464-1G>T

dbSNP: rs5030817

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853330	SCV002234896	pathogenic	Chuvash polycythemia; Von Hippel-Lindau syndrome	2023-06-24	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 223221). For these reasons, this variant has been classified as Pathogenic. 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. This variant is also known as c.677-1G>T. Disruption of this splice site has been observed in individuals with von Hippel-Lindau syndrome (PMID: 7987306, 8641976, 8707293, 17024664, 27439424, 33004005). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 2 of the VHL gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000208870	SCV000264749	pathogenic	Von Hippel-Lindau syndrome	2016-02-26	no assertion criteria provided	clinical testing
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV003329261	SCV004037029	not provided	not provided		no assertion provided	research