Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000735158 | SCV000863359 | likely pathogenic | not provided | 2018-09-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000735158 | SCV003524826 | pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 517 of the ABCB11 protein (p.Arg517His). This variant is present in population databases (rs760750012, gnomAD 0.008%). This missense change has been observed in individual(s) with cholestasis (PMID: 16641580, 27050426). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 598701). 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 expected to disrupt ABCB11 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCB11 function (PMID: 19101985). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000735158 | SCV004036367 | likely pathogenic | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19101985, 16641580, 24644547, 18395098, 27706244, 27050426) |
| Baylor Genetics | RCV003465671 | SCV004214375 | likely pathogenic | Benign recurrent intrahepatic cholestasis type 2 | 2023-12-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586912 | SCV005077686 | likely pathogenic | Progressive familial intrahepatic cholestasis | 2024-04-17 | criteria provided, single submitter | clinical testing | Variant summary: ABCB11 c.1550G>A (p.Arg517His) 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 1.2e-05 in 248502 control chromosomes (gnomAD). c.1550G>A has been reported in the literature in individuals affected with Familial Intrahepatic Cholestasis (Walkowiak_2006, Wang_2016). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in a loss of mature protein (Byrne_2009). The following publications have been ascertained in the context of this evaluation (PMID: 19101985, 16641580, 18395098, 27050426). ClinVar contains an entry for this variant (Variation ID: 598701). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005021143 | SCV005653430 | likely pathogenic | Benign recurrent intrahepatic cholestasis type 2; Progressive familial intrahepatic cholestasis type 2 | 2024-04-23 | criteria provided, single submitter | clinical testing |