ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.334T>A (p.Tyr112Asn) (rs104893824)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000002316 SCV000697499 pathogenic Von Hippel-Lindau syndrome 2016-02-03 criteria provided, single submitter clinical testing Variant summary: c.334T>A affects a conserved nucleotide, resulting in amino acid change from Tyr to Asn. 4/4 in-silico tools predict this variant to be damaging. This variant was not found in 91896 control chromosomes. This variant has been reported in multiple VHL pts with clear co-segregation of the variant with disease in the families (Bradley_1999 and Yoshida_2000). Functional studies showed that cell lines with variant have increased level of HIF2alpha (the critical oncogenic pVHL substrate in renal carcinogenesis) and its targets, the Y112N-producing cells formed large tumors (Li_2007), and the cell lines with variant showed disorganized fibroblast-like morphology and higher level of alpha5 integrin (Bangiyeva_2009). OMIM (also via ClinVar) lists this variant with classification of pathogenic. Taken together, this variant was classified as a Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000002316 SCV000897804 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
OMIM RCV000002316 SCV000022474 pathogenic Von Hippel-Lindau syndrome 1999-11-19 no assertion criteria provided literature only

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