Annotation Detail
Information
- Associated Genes
- VHL
- Associated Variants
-
VHL p.Arg64Pro (p.R64P)
(
ENST00000256474.3,
ENST00000345392.3,
ENST00000696143.2,
ENST00000696153.1,
ENST00000713811.1,
ENST00000713812.1,
ENST00000713815.1,
ENST00000713982.1 )
VHL p.Arg64Pro (p.R64P) ( ENST00000345392.3, ENST00000696143.2, ENST00000696153.1, ENST00000713811.1, ENST00000713812.1, ENST00000713815.1, ENST00000713982.1, ENST00000256474.3 ) - Associated Disease
- von Hippel-Lindau disease
- Source Database
- CIViC Evidence
- Description
- Molecular analysis of VHL gene in 146 probands, 103 with and 43 without a positive family history, resulted in the detection of 43 germline VHL mutations. Majority of mutations were found in patients with classic or multi-organ manifestations of VHL disease, but mutations were also found in patients with limited or single-organ manifestations of VHL disease. Follow-up of families with germline mutations and limited VHL manifestations was recommended. This missense mutation was found in a VHL type 2B family of 6 patients with the mutation, but incomplete penetrance (family no. 1; pedigree in Figure 2). A 59 yo carrier had no VHL manifestations but 2 unaffected children without the mutation and 2 children with the mutation, 1 with pheochromocytoma aged 32 and a 40 yo with no clinical manifestations. The 59 year old also had an affected family with the mutation - a parent (renal cell carcinoma) and a affected sibling (pheochromocytoma) and their child (paraganglioma) - and 4 unaffected siblings without the mutation. Only supporting evidence for pathogenicity because of cosegregation of the disease with multiple affected family in a gene definitively known to cause the disease (ACMG code: PP1).
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/5094
- Gene URL
- https://civic.genome.wustl.edu/links/genes/58
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1867
- Rating
- 3
- Evidence Type
- Predisposing
- Disease
- Von Hippel-Lindau Disease
- Evidence Direction
- Supports
- Evidence Level
- C
- Clinical Significance
- Uncertain Significance
- Pubmed
- 17661816
Drugs