ClinVar Miner

Submissions for variant NM_000443.4(ABCB4):c.3250C>T (p.Arg1084Trp)

dbSNP: rs1262922848
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000733103 SCV000861122 uncertain significance not provided 2018-05-04 criteria provided, single submitter clinical testing
Invitae RCV000733103 SCV002173627 uncertain significance not provided 2021-10-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1084 of the ABCB4 protein (p.Arg1084Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with low-phospholipid-associated cholelithiasis syndrome (PMID: 23533021, 32893960). ClinVar contains an entry for this variant (Variation ID: 597086). 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"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV004535866 SCV004117583 uncertain significance ABCB4-related disorder 2023-12-08 criteria provided, single submitter clinical testing The ABCB4 c.3250C>T variant is predicted to result in the amino acid substitution p.Arg1084Trp. This variant has been reported in several individuals with low phospholipid-associated cholelithiasis (LPAC) (Poupon et al 2013. PubMed ID: 23533021; Supplementary appendix, de Vries E et al 2020. PubMed ID: 32893960). This variant has not been reported in a large population database, indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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