Variant | Gene | Type | COSMIC ID | DNA Change (Coding Nucleotide) | Exon |
---|---|---|---|---|---|
VHL L188Q | VHL | missense | COSM17800 | 563T>A | 3 |
VHL copy number gain | VHL | CNV | |||
VHL copy number loss | VHL | CNV | |||
VHL any mutation | VHL | any | |||
VHL C162Y | VHL | missense | 3 | ||
VHL codon(s) 430 nonsense | VHL | nonsense | 3 |
The Von Hippel-Lindau (vHL) gene may be altered as a somatic (acquired) alteration and/or as a germline alteration associated with a rare autosomal dominant inherited cancer syndrome predisposing to a variety of malignant and benign tumors including clear cell renal cell carcinoma (ccRCC). The protein encoded by this gene is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. Biallelic VHL gene defects (truncation and missense) occur in approximately 75% of ccRCC cases. In addition, approximately 19% of tumors show evidence of inactivation by methylation of the VHL gene promoter. Studies of VHL mutational status as a prognostic marker in advanced sporadic RCC have been inconsistent. However, recent studies with VEGF-inhibitors suggested that loss of function mutations in VHL were associated with treatment response. There are ongoing clinical trials using the current VEGF-tyrosine kinase inhibitors specifically in patients with vHL. Correlation with clinical findings and genetic counseling may be helpful if there is clinical concern for an inherited cancer syndrome. Germline variants are not reported as part of the analysis for the whole exome sequencing assay for tumors.
This gene is a known cancer gene.
This gene is a known cancer gene.
The Von Hippel-Lindau (vHL) gene may be altered as a somatic (acquired) alteration and/or as a germline alteration associated with a rare autosomal dominant inherited cancer syndrome predisposing to a variety of malignant and benign tumors including clear cell renal cell carcinoma (ccRCC). The protein encoded by this gene is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. The VHL C162Y mutation has not been functionally or clinically validated. However, VHL C162F is known to be oncogenic, and therefore VHL C162Y is considered likely oncogenic. According to ClinVar, VHLC162F is also reported as a pathogenic germline variant (https://preview.ncbi.nlm.nih.gov/clinvar/variation/223225/). These results should be interpreted in the clinicopathologic context and appropriate germline genetic workup may be considered if clinically indicated.
The Von Hippel-Lindau (vHL) gene encodes a protein that is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. The VHL gene may be altered as a somatic (acquired) alteration and/or as a germline alteration associated with a rare autosomal dominant inherited cancer syndrome predisposing to a variety of malignant and benign tumors including clear cell renal cell carcinoma (ccRCC). Alterations in VHL have been reported in less than 1% of lung adenocarcinomas. The VHL p.G144* has been reported in multiple renal cell carcinomas as a somatic alteration. According to ClinVar, the VHL p.G144* is also reported as a pathogenic germline variant (https://www.ncbi.nlm.nih.gov/clinvar/variation/223208/). These results should be interpreted in the clinicopathologic context and appropriate germline genetic workup may be considered if clinically indicated.