ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.221T>A (p.Val74Asp)

dbSNP: rs5030803
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Total submissions: 2
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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 RCV000767236 SCV000897779 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001855961 SCV002291164 likely pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2021-11-12 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects VHL function (PMID: 21715564). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 625223). This missense change has been observed in individual(s) with clinical features of von Hippel-Lindau syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 74 of the VHL protein (p.Val74Asp).

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