ClinVar Miner

Submissions for variant NM_022437.3(ABCG8):c.55G>C (p.Asp19His) (rs11887534)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000266053 SCV000340356 benign not specified 2016-03-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000269126 SCV000430500 likely benign Sitosterolemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094725 SCV000483933 benign Sitosterolemia 1 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000808968 SCV000949102 risk factor not provided 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 19 of the ABCG8 protein (p.Asp19His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs11887534, ExAC 9%), including multiple homozygous individuals. Population-based case-control studies have shown that this variant is associated with reduced serum phytosterol levels and confers susceptibility to gallstone disease (PMID: 11893785, 17632509, 21039838, 21274884, 22898925). In a large meta-analysis with 4,381 cases and 3,765 controls (PMID: 22898925), individuals carrying this variant had an increased overall risk of gallstone disease (2.07, 95% CI: 1.65-2.60). ClinVar contains an entry for this variant (Variation ID: 4975). Experimental studies have shown that this missense causes a gain of ABCG8 protein function in vitro, contrary to the loss of ABCG8 protein function associated with sitosterolemia (PMID: 22898925). For these reasons, this variant has been classified as an Increased Risk Allele.
Mendelics RCV000269126 SCV001135671 benign Sitosterolemia 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000005263 SCV000025441 pathogenic Gallbladder disease 4 2007-08-01 no assertion criteria provided literature only

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