Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000267429 | SCV000344232 | uncertain significance | not provided | 2018-03-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000267429 | SCV003439979 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1161 of the ABCB4 protein (p.Pro1161Ser). This variant is present in population databases (rs121918442, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive cholestasis and/or low phospholipid associated cholelithiasis (PMID: 11313316, 12891548, 28587926). ClinVar contains an entry for this variant (Variation ID: 13692). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCB4 protein function. Experimental studies have shown that this missense change affects ABCB4 function (PMID: 28587926). 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. |
| Revvity Omics, |
RCV000267429 | SCV003813924 | likely pathogenic | not provided | 2022-07-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586009 | SCV005076604 | uncertain significance | not specified | 2024-04-24 | criteria provided, single submitter | clinical testing | Variant summary: ABCB4 c.3481C>T (p.Pro1161Ser) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251160 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3481C>T has been reported in the literature in individuals affected with Familial Intrahepatic Cholestasis (Rosmorduc_2003, Wang_2011, Poupon_2013) without evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Familial Intrahepatic Cholestasis. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a moderate decrease in secretion (Khabou_2017). The following publications have been ascertained in the context of this evaluation (PMID: 28587926, 19840255, 12891548, 20849526, 35741809). ClinVar contains an entry for this variant (Variation ID: 13692). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000014691 | SCV000034946 | pathogenic | Low phospholipid associated cholelithiasis | 2001-05-01 | no assertion criteria provided | literature only |