ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.194C>T (p.Ser65Leu)

dbSNP: rs5030826
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626711 SCV000747414 pathogenic Cerebellar hemangioblastoma; Pancreatic cysts; Retinal capillary hemangioma; Spinal hemangioblastoma 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001389259 SCV001590551 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-11-14 criteria provided, single submitter clinical testing This variant disrupts the p.Ser65 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 7987306, 22799452, 23384228). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects VHL function (PMID: 15611064). 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: 182975). This variant is also known as Ser136Leu. This missense change has been observed in individuals with clinical features of von Hippel-Lindau syndrome (PMID: 7987306, 10567493, 12114495, 22799452). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 65 of the VHL protein (p.Ser65Leu). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect - Invitae Patient Insights Network RCV001389259 SCV001749427 not provided Chuvash polycythemia; Von Hippel-Lindau syndrome no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 06-17-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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