ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.345C>A (p.His115Gln) (rs864622646)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588324 SCV000697502 pathogenic Von Hippel-Lindau syndrome 2016-02-05 criteria provided, single submitter clinical testing Variant summary: This c.345C>A affects a non-conserved nucleotide, resulting in amino acid change from His to Gln. 2/3 in-silico tools predict this variant to be damaging. The residue p.His115 is reported to be critical for interaction with HIF, thus this missense change is unlikely to be tolerated. By a structural/functional assay, interaction energy of residue was ~1.5 kcal/mol weaker than that with histidine in the wild type (Domene_2012), thus proving that the variant leads to functional impairment. This variant was not found in approximately 121600 control chromosomes, including the broad and large populations from ExAC. In literature, the p.His115Gln has been reported as a pathogenic variant found in >6 independent VHL patients/families, including somatic occurrences. At least one database calls this variant as pathogenic. Taken together, this variant has been classified as a Pathogenic.

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