Mutation of the proline P81 into a serine modifies the tumour suppressor function of the von Hippel–Lindau gene in the ccRCC

Chesnel, Franck; Jullion, Emmanuelle; Delalande, Olivier; Couturier, Antoine; Alusse, Adrien; Goff, Xavier Le; Lenglet, Marion; Gardie, Betty; Abadie, Caroline; Arlot‐Bonnemains, Yannick

doi:10.1038/s41416-022-01985-2

Cited by 3 publications

(1 citation statement)

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“…30 Futhermore, Chesnel et al demonstrated that the p.(P81S) variant affects the function of pVHL213 and provides invasiveness to the 786-O kidney cancer cell line. 31 We have classified this variant as LPV, taking into consideration its frequency among the probands in the mutation databases. The difficulty in these cases involving hypomorphous variants is to provide an appropriate follow-up for probands and their relatives, but no published recommendation exists, as far as we know.…”

Section: Cancer Geneticsmentioning

confidence: 99%

Update of the UMD-VHL database: classification of 164 challenging variants based on genotype–phenotype correlation among 605 entries

Mougel,

Mohamed,

Burnichon

et al. 2023

J Med Genet

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BackgroundThe von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations inVHLtumour suppressor gene. The identification ofVHLvariants requires accurate classification which has an impact on patient management and genetic counselling.MethodsThe TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collectedVHLgenetic variants and clinical characteristics of all VHL-suspected patients analysed from 2003 to 2021 by one of the nine laboratories performingVHLgenetic testing in France. Identified variants were registered in a locus-specific database, the Universal Mutation Database-VHL database (http://www.umd.be/VHL/).ResultsHere we report the expert classification of 164 variants, including all missense variants (n=124), all difficult interpretation variants (n=40) and their associated phenotypes. After initial American College of Medical Genetics classification, first-round classification was performed by the VHL expert group followed by a second round for discordant and ambiguous cases. Overall, the VHL experts modified the classification of 87 variants including 30 variants of uncertain significance that were as (likely)pathogenic variants for 19, and as likely benign for 11.ConclusionConsequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review.

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Section: Cancer Geneticsmentioning

confidence: 99%