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
- 49 family members from three generations of a Turkish family were examined. A clinical presentation of VHL type 2B was noted. Genetic testing was performed on 17 family members. 11 members with the mutation had manifestations, while 6 members with the mutation were asymptomatic. 1 of the asymptomatic individuals belonged to generation 2, while the remaining 5 belonged to the fourth generation, suggesting they may be too young to present manifestations. From the members that had manifestations: 9 had pheochromocytoma (5 bilateral), 1 had lumbar spine hemangioblastoma, 1 had retinal hemangioblastoma, 4 had renal cell carcinoma (2 bilateral), and 3 had pancreatic neuroendocrine tumours (1 also had a serous cystadenoma in addition to the neuroendocrine tumour). ACMG evidence codes: 'PP1' because of segregation results, 'PP2' because there is a missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease, 'PP4' because the patient's phenotype or family history is highly specific for a disease with a single genetic etiology. Relevant HPO terms: Renal cell carcinoma, Spinal hemangioblastoma, Multiple pancreatic cysts, Pheochromocytoma, Neuroendocrine neoplasm, Retinal hemangioblastoma.
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/5679
- Gene URL
- https://civic.genome.wustl.edu/links/genes/58
- Variant URL
- https://civic.genome.wustl.edu/links/variants/820
- Rating
- 3
- Evidence Type
- Predisposing
- Disease
- Von Hippel-Lindau Disease
- Evidence Direction
- Supports
- Evidence Level
- C
- Clinical Significance
- Uncertain Significance
- Pubmed
- 23673869
Drugs