ClinVar

Description

The VHL c.154G>A variant is predicted to result in the amino acid substitution p.Glu52Lys. This variant has been reported in patients with von Hippel-Lindau disease with and without renal involvement (Dollfus et al. 2002. PubMed ID: 12202531; Supplementary Table S1, Gallou et al. 2004. PubMed ID: 15300849). In addition, this variant has been identified and classified as a variant of uncertain significance in a study analyzing incidental findings in patients of European and African-ancestry that participated in the National Heart, Lung, and Blood Institute Exome Sequencing Project (Supplementary Table 1, Amendola et al. 2015. PubMed ID: 25637381; Supplementary Table 1, Dorschner et al. 2013. PubMed ID: 24055113). This variant has also been reported in an individual with hepatoblastoma (Aguiar et al. 2022. PubMed ID: 35495172). However, this variant is reported in 0.075% of alleles in individuals of African descent in gnomAD, which may be too common to be a primary cause of disease. This variant has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/161402/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.