Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV001784546 | SCV002542284 | uncertain significance | not provided | 2021-09-07 | criteria provided, single submitter | clinical testing | |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003141927 | SCV003807260 | pathogenic | Progressive familial intrahepatic cholestasis type 3 | 2022-04-20 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 very strong, PS4 moderated, PM2 moderated |
| Prevention |
RCV004536044 | SCV004119787 | pathogenic | ABCB4-related disorder | 2024-02-12 | criteria provided, single submitter | clinical testing | The ABCB4 c.1015dupT variant is predicted to result in a frameshift and premature protein termination (p.Ser339Phefs*17). This variant has been reported in the heterozygous state in multiple individuals with low phospholipid associated cholelithiasis (Rosmorduc et al. 2003. PubMed ID: 12891548; Poupon et al. 2013. PubMed ID: 23533021; Turro et al. 2020. PubMed ID: 32581362; Table S1, de Vries et al. 2020. PubMed ID: 32893960). This variant is reported in 0.17% of alleles in individuals of European (Finnish) descent in gnomAD; however, this variant failed to pass quality control filters in the gnomAD data. Frameshift variants in ABCB4 are expected to be pathogenic. Given the evidence, we interpret this variant as pathogenic. |
| Invitae | RCV001784546 | SCV004294481 | pathogenic | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser339Phefs*17) in the ABCB4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB4 are known to be pathogenic (PMID: 17726488, 25755532). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with ABCB4-related conditions (PMID: 32581362, 32893960). ClinVar contains an entry for this variant (Variation ID: 812984). For these reasons, this variant has been classified as Pathogenic. |
| NIHR Bioresource Rare Diseases, |
RCV001003944 | SCV001161918 | pathogenic | Cholestasis, intrahepatic, of pregnancy, 3 | no assertion criteria provided | research |