ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.485_486delinsTT (p.Cys162Phe)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003812589 SCV004608241 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-09-13 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 162 of the VHL protein (p.Cys162Phe). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 9452032, 10458336, 20064270). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects VHL function (PMID: 10878807, 11331612, 19228690). This variant disrupts the p.Cys162 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 8634692, 8641976, 8956040, 9681856, 28052007). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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