Annotation Detail
Information
- Associated Genes
- VHL
- Associated Variants
-
VHL p.Ala149Ser (p.A149S)
(
ENST00000256474.3,
ENST00000345392.3,
ENST00000696143.2,
ENST00000696153.1,
ENST00000713811.1,
ENST00000713812.1,
ENST00000713815.1,
ENST00000713982.1 )
VHL p.Ala149Ser (p.A149S) ( 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
- Study of a large kindred with von Hippel-Lindau disease (VHLD) and pheochromocytoma (spread over four generations). 25 proven cases of VHLD and 17 cases with pheochromocytoma were identified. Mutation analysis was performed in 14 family members (7 affected, 7 unaffected). 11 cases had the same mutation resulting in a predicted amino acid substitution of A149S. The cases with mutation that appeared unaffected were all very young (before the likely age of onset). The three cases without the mutation that appeared unaffected were aged 18, 54, and 69. ACMG evidence codes: 'PP1' based on segregation results, 'PM5' because the authors describe a prior report of a similar mutation at the same site (A149T), 'PP2' because they observe a missense variant in gene where missense variants are common mechanism of disease, and 'PP4' because the patients phenotypes and family history are highly specific for a disease with single genetic etiology.
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1896
- Gene URL
- https://civic.genome.wustl.edu/links/genes/58
- Variant URL
- https://civic.genome.wustl.edu/links/variants/820
- Rating
- 4
- Evidence Type
- Predisposing
- Disease
- Von Hippel-Lindau Disease
- Evidence Direction
- Supports
- Evidence Level
- C
- Clinical Significance
- Uncertain Significance
- Pubmed
- 9435426
Drugs