Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV001785064 | SCV002018974 | pathogenic | not provided | 2019-08-30 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002272498 | SCV002557677 | pathogenic | Cholestasis, progressive familial intrahepatic, 4 | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with progressive familial intrahepatic cholestasis 4 (MIM#615878) (PMID: 24614073). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Highly variable disease expression has been reported in patients with progressive familial intrahepatic cholestasis 4 (PMID: 32089630). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, PMID: 32089630). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Neuberg Centre For Genomic Medicine, |
RCV002272498 | SCV005382410 | likely pathogenic | Cholestasis, progressive familial intrahepatic, 4 | 2023-05-20 | criteria provided, single submitter | clinical testing | The stop gained c.3325G>T (p.Glu1109Ter) variant in the TJP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0003%) in the gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. Loss of function variants have been previously reported to be disease causing. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. The nucleotide change c.3325G>T in TJP2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. this variant is present in the penultimate exon, however termination variants downstream t this position found to be pathogenic .(Sambrotta M et al., 2014).. For these reasons, this variant has been classified as likely pathogenic. |