ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.320G>A (p.Arg107His) (rs193922609)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492448 SCV000580972 pathogenic Hereditary cancer-predisposing syndrome 2015-08-13 criteria provided, single submitter clinical testing The p.R107H pathogenic mutation (also known as c.320G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 320. The arginine at codon 107 is replaced by histidine, an amino acid with highly similar properties.This alteration has been reported in a woman meeting clinical diagnostic criteria for VHL and segregated with disease in her family (BoedekerCC et al. JClinEndocrinolMetab. 2009 Jun;94(6):1938-44). In addition, three other alterations at the same codon (p.R107C, p.R107P and p.R107G) have been associated with VHL and pheochromocytoma(DandanellM et al.BMC Med. Genet. 2012 ; 13():54;Siu WK et al.Chin. Med. J. 2011 Jan; 124(2):237-41;StolleC et al.Hum.Mutat. 1998;12(6):417-23). Based on the available evidence to date, p.R107H is classified as a pathogenic mutation.<br />
Invitae RCV001379601 SCV001577428 likely pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-03-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 107 of the VHL protein (p.Arg107His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with VHL-related conditions (PMID: 19336503, 12202531, external communication). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 223184). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg107 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 12624160, 22799452, 21362373, 12000816, Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000208864 SCV000264706 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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