ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.293A>G (p.Tyr98Cys)

dbSNP: rs864321643
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001218807 SCV001390711 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-02-03 criteria provided, single submitter clinical testing This variant disrupts the p.Tyr98 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7759077, 10878807, 11331612, 11331613, 12510195, 16261165, 19763184, 21204227, 23840444, 25371412). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 223176). This variant is also known as 506A>G. This missense change has been observed in individuals with clinical features of Von Hippel-Lindau syndrome (PMID: 10761708, 12081237, 25720320, 25952756, 29871882; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 98 of the VHL protein (p.Tyr98Cys). For these reasons, this variant has been classified as Pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000208825 SCV000264696 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357107 SCV001552459 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genomics Labs, University Health Network RCV000208825 SCV001950155 likely pathogenic Von Hippel-Lindau syndrome 2021-01-25 no assertion criteria provided clinical testing

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