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NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

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Interpretation:
Conflicting interpretations of pathogenicity; other​

Pathogenic(2); Uncertain significance(1); Benign(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: May 27, 2021)
Last evaluated:
Jul 9, 2020
Accession:
VCV000012274.18
Variation ID:
12274
Description:
single nucleotide variant
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NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

Allele ID
27313
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q37.1
Genomic location
2: 233760973 (GRCh38) GRCh38 UCSC
2: 234669619 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000463.3:c.686C>A MANE Select NP_000454.1:p.Pro229Gln missense
NM_001072.4:c.862-6061C>A MANE Select
NM_007120.3:c.868-6061C>A MANE Select
... more HGVS
Protein change
P229Q
Other names
-
Canonical SPDI
NC_000002.12:233760972:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00280 (A)

Allele frequency
1000 Genomes Project 0.00280
Trans-Omics for Precision Medicine (TOPMed) 0.00142
Links
ClinGen: CA122068
UniProtKB: P22309#VAR_009505
OMIM: 191740.0010
dbSNP: rs35350960
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 19, 2020 RCV000147905.9
Conflicting interpretations of pathogenicity; other 4 criteria provided, conflicting interpretations Jul 9, 2020 RCV000299521.10
Pathogenic; Affects 2 no assertion criteria provided May 1, 2019 RCV000013062.27
Pathogenic 1 no assertion criteria provided Dec 1, 2007 RCV000013063.25
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
UGT1A - - - GRCh38 - 280
UGT1A1 - - GRCh38
GRCh37
1 251
UGT1A10 - - GRCh38
GRCh37
- 305
UGT1A3 - - GRCh38
GRCh37
- 258
UGT1A4 - - GRCh38
GRCh37
- 258
UGT1A5 - - GRCh38
GRCh37
- 266
UGT1A6 - - GRCh38
GRCh37
- 278
UGT1A7 - - GRCh38
GRCh37
- 300
UGT1A8 - - GRCh38
GRCh37
1 307
UGT1A9 - - GRCh38
GRCh37
- 303

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Benign
(Feb 08, 2013)
criteria provided, single submitter
Method: clinical testing
not specified
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin: germline
Genetic Services Laboratory, University of Chicago
Accession: SCV000195396.1
Submitted: (Sep 11, 2014)
other
(Sep 17, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Eurofins NTD LLC (GA)
Accession: SCV000344304.3
Submitted: (Sep 19, 2018)
Other databases
http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=UGT1A1
Number of individuals with the variant: 15
Zygosity: 1 Homozygote, 14 Single Heterozygote
Sex: mixed
Benign
(Dec 31, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV001111446.2
Submitted: (Jan 29, 2020)
Pathogenic
(Aug 18, 2019)
criteria provided, single submitter
Method: clinical testing
None
Affected status: unknown
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001156826.2
Submitted: (Dec 11, 2020)
Uncertain significance
(Jun 19, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Affected status: unknown
Allele origin: germline
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine
Accession: SCV001653054.1
Submitted: (May 27, 2021)
Publications:
PubMed (11)
Comment:
The p.Pro229Gln variant in UGT1A1 has been reported in the heterogygous and compound heterozygous state in numerous individuals with Gilbert syndrome or Crigler-Najjar syndrome type … (more)
Number of individuals with the variant: 1
Pathogenic
(Jul 09, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Affected status: unknown
Allele origin: germline
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV001714674.1
Submitted: (May 26, 2021)
Publications:
PubMed (3)
PubMed: 8528206252004977715297
Number of individuals with the variant: 1
Pathogenic
(May 01, 2019)
no assertion criteria provided
Method: case-control
None
Affected status: unknown
Allele origin: inherited
Difficult and Complicated Liver Diseases and Artificial Liver Center,Beijing You An Hospital, Capital Medical University
Accession: SCV001156254.1
Submitted: (Aug 07, 2019)
Number of individuals with the variant: 13
Age: 25-55 years
Sex: mixed
Ethnicity/Population group: Chinese
Affects
(Dec 01, 2007)
no assertion criteria provided
Method: literature only
GILBERT SYNDROME
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033308.2
Submitted: (Dec 30, 2010)
Publications:
PubMed (5)
PubMed: 169283585282066480579962151518004206
Comment on evidence:
This variant has been designated UGT1A1*27 (Mackenzie et al., 1997). In affected members of 2 presumably unrelated Japanese families with Gilbert syndrome (143500), Koiwai et … (more)
Pathogenic
(Dec 01, 2007)
no assertion criteria provided
Method: literature only
CRIGLER-NAJJAR SYNDROME, TYPE II
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033309.2
Submitted: (Dec 30, 2010)
Publications:
PubMed (5)
PubMed: 169283585282066480579962151518004206
Comment on evidence:
This variant has been designated UGT1A1*27 (Mackenzie et al., 1997). In affected members of 2 presumably unrelated Japanese families with Gilbert syndrome (143500), Koiwai et … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Analysis of the <i>UGT1A1</i> Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution. Mi XX BioMed research international 2019 PMID: 31467903
UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children: A retrospective analysis and quantitative correlation. Abuduxikuer K Medicine 2018 PMID: 30544479
Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II. Sun L Medicine 2017 PMID: 29137095
UGT1A1 sequence variants associated with risk of adult hyperbilirubinemia: a quantitative analysis. Chen Z Gene 2014 PMID: 25200497
Mutation Analysis in Crigler-Najjar Syndrome Type II-Case Report and Literature Review. Ranjan P Journal of clinical and experimental hepatology 2011 PMID: 25755387
Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Udomuksorn W Pharmacogenetics and genomics 2007 PMID: 18004206
Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects. Takeuchi K Journal of gastroenterology and hepatology 2004 PMID: 15304120
Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert's syndrome. Maruo Y Clinical genetics 2003 PMID: 14616765
Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Gagné JF Molecular pharmacology 2002 PMID: 12181437
Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II. Yamamoto K Journal of human genetics 1998 PMID: 9621515
Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase. Koiwai O Human molecular genetics 1995 PMID: 8528206
Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Aono S Lancet (London, England) 1995 PMID: 7715297
The cDNA sequence and expression of a variant 17 beta-hydroxysteroid UDP-glucuronosyltransferase. Mackenzie PI The Journal of biological chemistry 1990 PMID: 1692835
The molecular weights of UDP-glucuronyltransferase determined with radiation-inactivation analysis. A molecular model of bilirubin UDP-glucuronyltransferase. Peters WH The Journal of biological chemistry 1984 PMID: 6480579
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=UGT1A1 - - - -

Text-mined citations for rs35350960...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 07, 2022