ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.454A>C (p.Thr152Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193295 SCV001362034 uncertain significance not specified 2019-09-05 criteria provided, single submitter clinical testing Variant summary: VHL c.454A>C (p.Thr152Pro) results in a non-conservative amino acid change located in the von Hippel-Lindau disease tumor suppressor, alpha domain (IPR024048) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251496 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.454A>C, has been reported in the literature as a de novo variant in an individual affected with Von Hippel-Lindau Syndrome (Gijtenbeek_2005, Hes_2007). These data do not allow unequivocal conclusions about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Several missense variants affecting nearby residues (e.g. p.A149T, p.I151N, p.I151S, p.P154L, p.V155E) were reported in affected individuals (HGMD), suggesting the functional importance for the affected protein region. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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