ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.548C>T (p.Ser183Leu) (rs5030823)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476376 SCV000553414 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 183 of the VHL protein (p.Ser183Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs5030823, ExAC 0.002%). This variant has been reported in an individual affected with erythrocytosis and pulmonary arterial hypertension (PAH), and an individual affected with paraganglioma (PMID: 21454469, 24466223). ClinVar contains an entry for this variant (Variation ID: 411985). An experimental study has shown that this variant results in impaired VHL function, increased hypoxia-inducible factor (HIF) pathway activation, and unstable protein in vitro (PMID: 21454469, 30338240). 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.
OMIM RCV001007624 SCV001167312 pathogenic Erythrocytosis, familial, 2 2020-03-05 no assertion criteria provided literature only

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