ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.408T>G (p.Phe136Leu) (rs878854125)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563379 SCV000675807 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Invitae RCV000231504 SCV000285496 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 136 of the VHL protein (p.Phe136Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VHL-related disease. ClinVar contains an entry for this variant (Variation ID: 238107). Experimental in-vitro studies have shown that this missense change results in impaired folding, stability and function of the VHL protein (PMID: 23840444). However, the clinical significance of this finding is unclear. 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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