ClinVar Miner

Submissions for variant NM_001072.4(UGT1A6):c.1088C>T (p.Pro363Leu) (rs34946978)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194762 SCV000249367 likely pathogenic Hyperbilirubinemia 2014-09-22 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000300556 SCV000335445 other not provided 2018-08-23 criteria provided, single submitter clinical testing
GeneDx RCV000300556 SCV000521290 likely pathogenic not provided 2016-11-16 criteria provided, single submitter clinical testing The P364L variant in the UGT1A1 gene has been identified in the homozygous state and in the heterozygous state in individuals with Crigler-Najjar syndrome type II and Gilbert syndrome who were heterozygous for a second UGT1A1 variant (Takeuchi et al., 2004; Li et al., 2015; Yang et al., 2016). The P364L variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. However, P364L was observed with an allele frequency of 1.1% in individuals from East Asia (McVean et al., 2012). The P364L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Functional studies indicate that cells expressing P364L have 64% lower UGT1A1 enzyme activity compared to wild type (Takeuchi et al., 2004; Mimura et al., 2011). The P364L variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000056 SCV000884824 pathogenic none provided 2020-05-11 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763479 SCV000894262 likely pathogenic Bilirubin, serum level of, quantitative trait locus 1; Crigler-Najjar syndrome type 1; Lucey-Driscoll syndrome; Crigler-Najjar syndrome, type II; Gilbert syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000300556 SCV001115248 benign not provided 2020-11-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000999562 SCV001297726 uncertain significance Gilbert syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centogene AG - the Rare Disease Company RCV001250229 SCV001424510 pathogenic Crigler-Najjar syndrome type 1 criteria provided, single submitter clinical testing
Difficult and Complicated Liver Diseases and Artificial Liver Center,Beijing You An Hospital, Capital Medical University RCV000999562 SCV001156258 pathogenic Gilbert syndrome 2019-05-01 no assertion criteria provided case-control

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