ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.232A>G (p.Asn78Asp)

dbSNP: rs869025621
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Total submissions: 4
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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 RCV000767241 SCV000897784 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001869052 SCV002130749 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-04-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn78 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 8956040, 12114495, 15109448, 15300849, 19464396, 23842656). 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: 625226). This missense change has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 23224817). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 78 of the VHL protein (p.Asn78Asp).
GeneDx RCV002260666 SCV002540545 likely pathogenic not provided 2022-06-30 criteria provided, single submitter clinical testing Observed in individuals meeting diagnostic criteria of von Hippel-Lindau syndrome and segregated with disease in one family (Cingoz 2013, Lee 2016); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20233476, 24727139, 23842656, 7728151, 12114495, 15300849, 8956040, 15109448, 27439424, 23224817)
Clinical Genomics Labs, University Health Network RCV000767241 SCV001950136 likely pathogenic Von Hippel-Lindau syndrome 2018-08-08 no assertion criteria provided clinical testing

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