ClinVar Miner

Submissions for variant NM_003742.4(ABCB11):c.1460G>A (p.Arg487His) (rs188824058)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000396656 SCV000344575 likely pathogenic not provided 2017-10-03 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000761414 SCV000891472 uncertain significance Progressive familial intrahepatic cholestasis 2 2017-12-30 criteria provided, single submitter curation
Fulgent Genetics,Fulgent Genetics RCV000763465 SCV000894242 likely pathogenic Benign recurrent intrahepatic cholestasis type 2; Progressive familial intrahepatic cholestasis 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000396656 SCV000959798 likely pathogenic not provided 2020-09-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 487 of the ABCB11 protein (p.Arg487His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs188824058, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with chronic cholestasis (PMID: 12717091, 27050426). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 290081). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg487 amino acid residue in ABCB11. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 12717091, 27050426, 18395098), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003929 SCV001161903 likely pathogenic Cholestasis, intrahepatic, of pregnancy 3 no assertion criteria provided research

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