ClinVar Miner

Submissions for variant NM_022437.3(ABCG8):c.1285A>G (p.Met429Val)

dbSNP: rs147194762
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596406 SCV000705663 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001137121 SCV001297025 benign Sitosterolemia 1 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Invitae RCV000596406 SCV001657461 likely benign not provided 2024-01-18 criteria provided, single submitter clinical testing
GeneDx RCV000596406 SCV002504438 likely benign not provided 2019-10-08 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003330815 SCV004039551 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing Variant summary: ABCG8 c.1285A>G (p.Met429Val) results in a conservative amino acid change located in the ABC-2 type transporter, transmembrane domain (IPR013525) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 251444 control chromosomes, predominantly at a frequency of 0.004 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.05-fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG8 causing Sitosterolemia phenotype (0.0038), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.1285A>G has been reported in the literature in East Asian individuals affected with Sitosterolemia or familial hypercholesterolemia without strong evidence of causality (e.g. Pek_2018, Miwa_2005, Tada_2018, Tada_2018b, Tada_2022, Kojima_2020, Nomura_2020). These reports do not provide unequivocal conclusions about association of the variant with Sitosterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29353225, 15816807, 30241732, 32275988, 32862661, 32088153, 35248527, 30007774). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n=1), benign (n=1) or likely benign (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Revvity Omics, Revvity RCV001137121 SCV004238907 uncertain significance Sitosterolemia 1 2023-09-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003952976 SCV004782456 likely benign ABCG8-related disorder 2023-10-01 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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