Submissions for variant NM_000463.3(UGT1A1):c.964A>G (p.Ile322Val)

dbSNP: rs200903749

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000898514	SCV001042724	benign	not provided	2023-12-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001142512	SCV001302958	uncertain significance	Lucey-Driscoll 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001142513	SCV001302959	benign	Crigler-Najjar 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001142514	SCV001302960	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000898514	SCV002049186	uncertain significance	not provided	2021-01-05	criteria provided, single submitter	clinical testing	The UGT1A1 c.964A>G; p.Ile322Val variant (rs200903749) is reported in the heterozygous state in 7 individuals with Gilbert syndrome and in the homozygous state in one individual with Gilbert syndrome; however, this variant was also identified in 6 healthy controls (Farheen 2006). This variant has also been reported in cis to the pathogenic-mild (TA)7 promoter variant in one individual with inherited unconjugated hyperbilirubinemia (Zubaida 2019). The p.Ile322Val variant is reported in ClinVar (Variation ID: 724578). It is found in the South Asian general population with an allele frequency of 1.5% (446/30616 alleles, including 6 homozygotes) in the Genome Aggregation Database. The isoleucine at codon 322 is moderately conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.35). Based on available information, the clinical significance of this variant is uncertain at this time. REFERENCES Farheen S et al. Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol. 2006 Apr 14;12(14):2269-75. Zubaida B et al. Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias. Clin Biochem. 2019 Jul;69:30-35.
Mayo Clinic Laboratories, Mayo Clinic	RCV000898514	SCV004226026	uncertain significance	not provided	2022-03-04	criteria provided, single submitter	clinical testing