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
- A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. A mutation c.194C>T (p.Ser65Leu) was found in 3 families (#4, #5, #6) with 11 genetically confirmed patients and 13 affected members in total. From family #4: one male patient presented with renal cell carcinoma at 33Y and pancreatic cysts or tumors at 33Y (mutation confirmed). From family #5: male proband with CNS haemangioblastoma at 21Y and multpile pancreatic cysts or tumours at 30Y (mutation confirmed), grandfather with CNS haemangioblastoma at 30Y (mutation status unknown), father with CNS haemangioblastoma at 36Y (mutation status unknown), and uncle with CNS haemangioblastoma at 33Y (mutation status unknown). From family #6: female proband with RCC at 36Y who then developed PCT at 37Y (mutation confirmed); daughter confirmed with the mutation but no manifestations and age unknown; mother with CNS hemangioblastoma diagnosed at 59Y (mutation confirmed); uncle 1 with CNS hemangioblastoma at 45Y, renal cell carcinoma at 59Y, and multiple pancreatic cysts or tumours at 65Y (mutation confirmed); son of uncle 1 with CNS hemangioblastoma at 22Y (mutation status unknown); Uncle 2 with CNS hemangioblastoma at 51Y, renal cell carcinoma at 51Y, and pancreatic cysts or tumours at 51Y (mutation status unknown); 1st son of uncle 2 with CNS hemangioblastoma at 22Y, renal cell carcinoma at 30Y, and pancreatic cysts or tumours at 31Y (mutation confirmed); 2nd son of uncle 2 with mutation confirmed but no manifestations and age unknown; granddaughter of uncle 2 with mutation confirmed but no manifestations and age unknown; Uncle 3 with multiple pancreatic cysts or tumours at 49Y (mutation confirmed); Aunt with CNS hemangioblastoma at 53Y and retinal angioma at 53Y (mutation confirmed). This evidence supports the following ACMG Codes: PP4 - the patient's phenotype and family history are highly specific for a disease with single genetic etiology, PP1- Co-segregation with disease in multiple affected family members (.e. family #6), PM2 - Absent from controls (i.e. gnomAD)
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6791
- Gene URL
- https://civic.genome.wustl.edu/links/genes/58
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1788
- Rating
- 3
- Evidence Type
- Predisposing
- Disease
- Von Hippel-Lindau Disease
- Evidence Direction
- Supports
- Evidence Level
- C
- Clinical Significance
- Uncertain Significance
- Pubmed
- 28388566
Drugs