ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.429C>T (p.Asp143=) (rs773556807)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470382 SCV000563217 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change affects codon 143 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 present in population databases (rs773556807, ExAC 0.001%). This variant has been observed to be homozygous or in combination with another VHL variant in several individuals affected with erythrocytosis (PMID: 29891534). This variant is also known as D143D in the literature. ClinVar contains an entry for this variant (Variation ID: 416990). Experimental studies using both patient-derived RNA and minigene assays have shown that this silent change causes an increase of an alternative transcript, with skipping of exon 2 (PMID: 29891534). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000564320 SCV000664611 likely benign Hereditary cancer-predisposing syndrome 2016-01-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000613763 SCV000714522 likely benign not specified 2018-01-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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