ClinVar Miner

Submissions for variant NM_018849.3(ABCB4):c.1769G>A (p.Arg590Gln) (rs45575636)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723739 SCV000226227 uncertain significance not provided 2018-04-10 criteria provided, single submitter clinical testing
GeneDx RCV000249752 SCV000490387 uncertain significance not specified 2016-10-05 criteria provided, single submitter clinical testing The R590Q variant in the ABCB4 gene has previously been reported in association with ABCB4-related disorders including low phospholipid-associated cholelithiasis, primary sclerosing cholangitis, and anicteric cholestasis in several individuals who were heterozygous for R590Q alone, homozygous for R590Q, or heterozygous for R590Q and another variant in the ABCB4 gene (Degiorgio et al., 2007; Ziol et al., 2008; Colombo et al., 2011; Poupon et al., 2013; Degiorgio et al., 2015). However, the NHLBI Exome Sequencing Project and the 1000 Genomes Project Consortium reports that R590Q was identified in 74/8600 (0.9%) alleles from individuals of European background and in 8/198 (4%) of alleles from the Luhya population in Webuye, Kenya indicating it may be a rare, benign variant in these populations. The R590Q 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (H589Y, L591Q, T593A/M) have been reported in the Human Gene Mutation Database in association with ABCB4-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
GenomeConnect, ClinGen RCV000709935 SCV000840292 not provided ABCB4-related disorders no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662150 SCV000784493 uncertain significance Progressive familial intrahepatic cholestasis 3 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000014696 SCV000784494 uncertain significance Cholestasis, intrahepatic, of pregnancy 3 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000033067 SCV000784495 uncertain significance Cholecystitis 2018-03-05 criteria provided, single submitter clinical testing
OMIM RCV000014696 SCV000034951 pathogenic Cholestasis, intrahepatic, of pregnancy 3 2009-10-01 no assertion criteria provided literature only
OMIM RCV000033067 SCV000056847 pathogenic Cholecystitis 2009-10-01 no assertion criteria provided literature only
PreventionGenetics RCV000249752 SCV000304284 likely benign not specified criteria provided, single submitter clinical testing

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