Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003037234 | SCV003440035 | uncertain significance | not provided | 2022-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 954 of the ABCB4 protein (p.Gly954Ser). This variant is present in population databases (rs779829759, gnomAD 0.002%). This missense change has been observed in individuals with clinical features of progressive familial intrahepatic cholestasis (PMID: 17726488, 29761167, 33763395, 34016879). 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: "Benign"; Align-GVGD: "Class C0"). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ABCB4 function (PMID: 26474921). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 |
RCV003037234 | SCV004010678 | likely pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | ABCB4: PM2, PM3, PP4, PS3:Supporting |
Rolfs Rare Disease Consulting, |
RCV003485807 | SCV004232489 | pathogenic | Progressive familial intrahepatic cholestasis type 3 | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003037234 | SCV004238846 | uncertain significance | not provided | 2023-11-22 | criteria provided, single submitter | clinical testing |