ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.239G>T (p.Ser80Ile)

dbSNP: rs5030805
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000767244 SCV000897787 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001220559 SCV001392556 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2021-12-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser80 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9215674, 12500216; Invitae). 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: 625229). This variant is also known as c.452G>T. This missense change has been observed in individual(s) with Von Hippel-Lindau disease (PMID: 7728151, 19763184, 24678776, 27527340, 29871882). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 80 of the VHL protein (p.Ser80Ile).
Clinical Genomics Labs, University Health Network RCV000767244 SCV001950145 likely pathogenic Von Hippel-Lindau syndrome 2016-05-30 no assertion criteria provided clinical testing

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