Annotation Detail

Information
Associated Genes
VHL
Associated Variants
VHL p.Ser65Leu (p.S65L) ( ENST00000256474.3, ENST00000345392.3, ENST00000696143.2, ENST00000696153.1, ENST00000713811.1, ENST00000713812.1, ENST00000713815.1, ENST00000713982.1 )
VHL p.Ser65Leu (p.S65L) ( 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
Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. This missense mutation was found in 4 VHL families of 11 patients altogether. Ten had retinal hemangioblastomas, 4 had cerebellar hemangioblastomas, and 2 had renal cell carcinoma. ACMG codes as follows: supporting evidence for pathogenicity because of cosegregation of disease with multiple affected family members in a gene definitively known to cause the disease (ACMG code: PP1). Two other amino acid changes at this site were also reported in this publication in association with disease (S65W and S65P). Relevant HPO terms: Cerebellar hemangioblastoma, Retinal hemangioblastoma, Renal cell carcinoma.
Variant Origin
germline
Variant Origin
Rare Germline
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/5159
Gene URL
https://civic.genome.wustl.edu/links/genes/58
Variant URL
https://civic.genome.wustl.edu/links/variants/1788
Rating
2
Evidence Type
Predisposing
Disease
Von Hippel-Lindau Disease
Evidence Direction
Supports
Evidence Level
C
Clinical Significance
Uncertain Significance
Pubmed
17024664
Drugs