ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.277G>C (p.Gly93Arg) (rs5030808)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001035237 SCV001198557 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 93 of the VHL protein (p.Gly93Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with VHL-related conditions (PMID: 20660572, 23660872). This variant is also known as 490G>C (p.Gly93Arg) or c.277G>C (p.GLy39Arg) in the literature. ClinVar contains an entry for this variant (Variation ID: 223174). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Gly93 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID:12000816, 9329368, 8707293, 17922902, 17661816), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208861 SCV000264692 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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