ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.382C>T (p.Leu128Phe) (rs1553619956)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586899 SCV000697507 uncertain significance not provided 2016-02-05 criteria provided, single submitter clinical testing
Invitae RCV001232610 SCV001405174 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-07-23 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 128 of the VHL protein (p.Leu128Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals affected with von Hippel-Lindau syndrome and pheochromocytoma (PMID: 8956040, 9681856, Invitae). This variant is also known as c.595C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 496060). This variant has been reported to have conflicting or insufficient data to determine the effect on VHL protein function (PMID: 11865071, 21685897). This variant disrupts the p.Leu128 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 19270817, 14722919, 17024664), 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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