Annotation Detail

Information
Associated Genes
VHL
Associated Variants
VHL p.Arg167Trp (p.R167W) ( ENST00000256474.3, ENST00000345392.3, ENST00000696143.2, ENST00000696153.1, ENST00000713811.1, ENST00000713812.1, ENST00000713815.1, ENST00000713982.1 )
VHL p.Arg167Trp (p.R167W) ( ENST00000256474.3, ENST00000345392.3, ENST00000696143.2, ENST00000696153.1, ENST00000713811.1, ENST00000713812.1, ENST00000713815.1, ENST00000713982.1 )
Associated Disease
von Hippel-Lindau disease
Source Database
CIViC Evidence
Description
In a study of 114 unrelated VHL families, 85 germline mutations were found. VHL mutations were detected in affected family members, but not in unaffected family members or 96 normal individuals. This missense mutation was found in four VHL type 2 families of 51 individuals altogether (family IDs 2338, 3490, 4477, 4405). 36 of 51 individuals had retinal hemangioblastomas, 17 had cerebellar hemangioblastomas, 16 with renal cell carcinoma, and 36 with pheochromocytomas. This mutation was also detected in a VHL type 1 patient with angiomas (family ID 3699). Supporting evidence of pathogenicity because cosegregation with disease in multiple affected family members 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/4912
Gene URL
https://civic.genome.wustl.edu/links/genes/58
Variant URL
https://civic.genome.wustl.edu/links/variants/1747
Rating
4
Evidence Type
Predisposing
Disease
Von Hippel-Lindau Disease
Evidence Direction
Supports
Evidence Level
C
Clinical Significance
Uncertain Significance
Pubmed
7728151
Drugs