ClinVar Miner

Submissions for variant UGT1A1*6 (rs4148323)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000173139 SCV000224228 likely benign not specified 2014-07-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000013071 SCV000249368 other Gilbert's syndrome 2016-01-25 no assertion criteria provided clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000013071 SCV000428642 likely benign Gilbert's syndrome 2016-06-14 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000013071 SCV000538072 likely pathogenic Gilbert's syndrome 2016-03-30 criteria provided, single submitter clinical testing The c.211G>A (p.Gly71Arg) missense variant in the UGT1A1 gene is a known common variant associated with Gilbert Syndrome and hyperbilirubinemia in individuals of East Asian descent. Numerous case-control studies have demonstrated this variant is significantly prevalent in affected individuals relative to unaffected controls (Fu and Liu, 2005; Lin et al., 2009; Zhou et al., 2009; Prachukthum et al., 2009; Gao et al., 2010; Long et al., 2011a; Long et al., 2011b; Chen et al., 2014). Multiple in vitro studies have shown that this variant leads to reduced enzymatic activity, and this variant is associated with elevated serum bilirubin in infants (Yamamoto et al., 1998; Sneitz et al., 2010; Chou et al., 2011). The allele frequency is high in the population databases for individuals of East Asian descent, which is expected given the high prevalence of the disease (1000 Genomes = 13.8% [EAS]; ExAC = 15.24% [EAS]). Hence, a yet unknown genetic modifier that is specific to the East Asian population may contribute to the high disease prevalence. Finally, a reputable clinical diagnostic laboratory has reported this variant as Likely Pathogenic (University of Chicago). Together, this collective evidence supports the classification of the c.211G>A (p.Gly71Arg) as a Likely Pathogenic variant for Gilbert Syndrome.
Medical Genetics Summaries RCV000664403 SCV000788335 drug response Irinotecan response 2018-04-04 criteria provided, single submitter curation UGT1A1*6 appears to be an important predictor of severe toxicity to irinotecan therapy in Asian populations. In Japan, a reduced dose of irinotecan is recommended for individuals with UGT1A1 *6/*6, *6/*28, and *28/*28 genotypes.
OMIM RCV000013071 SCV000033317 affects Gilbert's syndrome 2013-01-01 no assertion criteria provided literature only
OMIM RCV000022810 SCV000044099 pathogenic Lucey-Driscoll syndrome 2013-01-01 no assertion criteria provided literature only
OMIM RCV000022811 SCV000044100 association Bilirubin, serum level of, quantitative trait locus 1 2013-01-01 no assertion criteria provided literature only
PharmGKB RCV000211162 SCV000268322 drug response irinotecan response - Other 2017-08-28 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
PharmGKB RCV000211250 SCV000268323 drug response SN-38 response - Other 2016-07-11 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
PreventionGenetics RCV000173139 SCV000304405 benign not specified criteria provided, single submitter clinical testing

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