ClinVar

Description

The c.278_279delGCinsTT variant (also known as p.G93V), located in coding exon 1 of the VHL gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 278 to 279. This results in the substitution of the glycine residue for a valine residue at codon 93, an amino acid with dissimilar properties. An variant resulting in the same amino acid substitution, p.G93V (c.278G>T), has been reported in a cohort of patients with non-syndromic pheochromocytoma (Neumann HP et al. N. Engl. J. Med., 2002 May;346:1459-66). Further, other missense variants at this codon (p.G93D, p.G93S, p.G93R, p.G93C) have been reported in numerous individuals with personal and/or family history consistent with Von Hippel-Lindau syndrome (VHL) (Chen F et al. Hum. Mutat., 1995;5:66-75; Zbar B et al. Hum. Mutat., 1996;8:348-57; Glavac D et al. Hum. Genet., 1996 Sep;98:271-80; Neumann HP et al. N. Engl. J. Med., 2002 May;346:1459-66; Klein B et al. Hum. Genet., 2001 May;108:376-84; Schreinemakers JM et al. World J Surg Oncol, 2007 Oct;5:112; Iacobone M et al. Surgery, 2011 Dec;150:1194-201). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.