Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000731136 | SCV000858914 | uncertain significance | not provided | 2017-12-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779070 | SCV002015019 | uncertain significance | not specified | 2021-10-22 | criteria provided, single submitter | clinical testing | Variant summary: ABCB11 c.2191C>T (p.Pro731Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00046 in 247478 control chromosomes (gnomAD and publication). This frequency is not significantly higher than expected for a pathogenic variant in ABCB11 causing Familial Intrahepatic Cholestasis (0.00046 vs 0.0022), allowing no conclusion about variant significance. c.2191C>T has been reported in the literature in individuals affected with Familial Intrahepatic Cholestasis (Anzivino_2012, Goldschmidt_2015). These reports do not provide unequivocal conclusions about association of the variant with Familial Intrahepatic Cholestasis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV000731136 | SCV003276626 | uncertain significance | not provided | 2022-08-12 | 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 731 of the ABCB11 protein (p.Pro731Ser). This variant is present in population databases (rs201240844, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with cholestasis of pregnancy (PMID: 23022423). ClinVar contains an entry for this variant (Variation ID: 595557). 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) performed at Invitae indicates that this missense variant is not expected to disrupt ABCB11 protein function. 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. |
Ce |
RCV000731136 | SCV004700846 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | ABCB11: PM2:Supporting, BP4 |
NIHR Bioresource Rare Diseases, |
RCV001003552 | SCV001161896 | likely pathogenic | Cholestasis, intrahepatic, of pregnancy, 3 | no assertion criteria provided | research |