Table 2.

Molecular Genetic Testing Used in von Hippel-Lindau Syndrome

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
VHL Sequence analysis 3, 4~85% 5, 6
Gene-targeted deletion/duplication analysis 7~10% 5, 6
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Sequence analysis of intron 1 should be performed in probands without an identified VHL pathogenic variant in the coding region; intron 1 pathogenic variants can lead to inclusion of a cryptic exon (designated exon E1') [Lenglet et al 2018].

5.

Nordstrom-O'Brien et al [2010] and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

6.

Approximately 5% of individuals with a clinical diagnosis of von Hippel-Lindau syndrome do not have a pathogenic variant identified.

7.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

From: Von Hippel-Lindau Syndrome

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