ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.365C>T (p.Ala122Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001327637 SCV001518722 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 122 of the VHL protein (p.Ala122Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of von Hippel-Lindau syndrome (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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