ClinVar Miner

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

gnomAD frequency: 0.06566  dbSNP: rs11887534
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000266053 SCV000340356 benign not specified 2016-03-16 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000269126 SCV000430500 likely benign Sitosterolemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, 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 RCV001705581 SCV000949102 association not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 19 of the ABCG8 protein (p.Asp19His). This variant is present in population databases (rs11887534, gnomAD 10%), including at least one homozygous and/or hemizygous individual. 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). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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). In summary, this is a common variant that is associated with an increased risk for developing disease. 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
GeneDx RCV001705581 SCV001841286 benign not provided 2018-07-05 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29764733, 31327807, 30975109, 30036524, 11893785, 17632509, 20581104, 21039838, 22898925, 20163776, 20592455, 22675952, 20170916)
Ambry Genetics RCV002345232 SCV002648864 benign Cardiovascular phenotype 2018-12-03 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002490320 SCV002796617 likely benign Sitosterolemia 2 2021-09-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000266053 SCV004029676 likely benign not specified 2023-07-17 criteria provided, single submitter clinical testing
OMIM RCV000005263 SCV000025441 pathogenic Gallbladder disease 4 2007-08-01 no assertion criteria provided literature only
Clinical Genetics, Academic Medical Center RCV000266053 SCV001918137 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000266053 SCV001929981 benign not specified no assertion criteria provided clinical testing

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