Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036542 | SCV000060197 | pathogenic | Von Hippel-Lindau syndrome | 2015-03-20 | criteria provided, single submitter | clinical testing | The p.Arg107Gly variant in VHL has been reported as a de novo (paternity confirm ed) occurrence in 1 child with nonsyndromic pheochromocytomas (Neumann 2002). In addition, it was identified in 2 children with von Hippel-Lindau (VHL) syndrome and segregated with disease in 4 affected family members from 2 families (Siu 2 011, LMM unpublished data). Of note, other variants at this position (p.Arg107Hi s, p.Arg107Pro) have been reported in individuals with VHL, suggesting that an a lteration at this position is not tolerated. In summary, this variant meets our criteria to be classified as pathogenic for VHL in an autosomal dominant manner (http://www.partners.org/personalizedmedicine/LMM) based upon a de novo occurren ce and segregation studies. |
| Fulgent Genetics, |
RCV000763091 | SCV000893625 | likely pathogenic | Chuvash polycythemia; Pheochromocytoma; Von Hippel-Lindau syndrome; Nonpapillary renal cell carcinoma | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002321506 | SCV002610818 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2014-12-10 | criteria provided, single submitter | clinical testing | The p.R107G variant (also known as c.319C>G), located in coding exon 1 of the VHL gene, results from a C to G substitution at nucleotide position 319. The arginine at codon 107 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been previously identified in individuals with CNS hemangioblastoma and one individual with isolated pheochromocytoma (Siu WK, Chin. Med. J. 2011 Jan; 124(2):237-41. Neumann HP, N. Engl. J. Med. 2002 May; 346(19):1459-66; Ambry Internal Data). In addition, three other mutations (p.R107C, p.R107H and p.R107P) in the same codon have been associated with VHL and pheochromocytoma. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5215 samples (10430 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 4300 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |