ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.203C>T (p.Ser68Leu) (rs869025617)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000767234 SCV000897777 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001046095 SCV001209983 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 68 of the VHL protein (p.Ser68Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of VHL (Invitae). ClinVar contains an entry for this variant (Variation ID: 625222). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant disrupts the p.Ser68 amino acid residue in VHL. Other variants that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 27785399, 17661816, 12000816, 10627136), which suggests that this may be a clinically significant amino acid residue. 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.

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