Submissions for variant NM_139027.6(ADAMTS13):c.1169G>A (p.Trp390Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV002468903	SCV002765136	pathogenic	Upshaw-Schulman syndrome	2022-12-20	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002468903	SCV003921795	pathogenic	Upshaw-Schulman syndrome	2021-05-06	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, 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 thrombotic thrombocytopenic purpura, hereditary (MIM#274150). (I) 0106 - This gene is associated with autosomal recessive disease. (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) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (SP) 0701 - Other premature termination variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. More than nine other NMD-predicted variants have been reported as likely pathogenic/pathogenic (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. It has been reported in two individuals with congenital thrombotic thrombocytopenic purpura (cTTP) (PMIDs: 12393505, 30792199). (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign