ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.414A>G (p.Pro138=) (rs869025648)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216698 SCV000276962 pathogenic Hereditary cancer-predisposing syndrome 2018-12-20 criteria provided, single submitter clinical testing Functionally-validated splicing mutation;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Strong segregation with disease (lod >3 = >10 meioses)
Invitae RCV000469600 SCV000553422 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change affects codon 138 of the VHL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the VHL protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with von Hippel-Lindau (VHL) syndrome-associated tumors in several families (PMID: 29891534). This variant has also been observed in individuals with a personal and/or family history of VHL syndrome-associated tumors (Invitae). This variant is also known as P138P in the literature. ClinVar contains an entry for this variant (Variation ID: 223206). Experimental studies have shown that this silent change causes an increase of the alternative VHL transcript with skipping of exon 2 in both patient-derived cells and minigene assays (PMID: 29891534). For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208865 SCV000264732 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing
OMIM RCV000208865 SCV001167313 pathogenic Von Hippel-Lindau syndrome 2020-03-05 no assertion criteria provided literature only

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