Submissions for variant NM_001011551.3(C1GALT1C1):c.266C>T (p.Thr89Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
The Morris Kahn Laboratory of Human Genetics, Ben-Gurion University of the Negev	RCV003236752	SCV003935146	pathogenic	Atypical hemolytic-uremic syndrome	2023-06-24	criteria provided, single submitter	research	A de novo C1GALT1C1:c.266C>T;p.Thr89Ile variant was identified in a patient exhibiting early-onset atypical hemolytic uremic syndrome (aHUS), and was not present in the gnomAD database. This variant is situated in an area of remarkable evolutionary conservation. In vitro studies have demonstrated that this variant results in the generation of an exposed T-antigen on erythrocytes, which incites complement activation against these erythrocytes (Noam Hadar et al. 2023). This action potentially mirrors the mechanism of T-antigen mediated pneumococcal hemolytic uremic syndrome (Nicolas Burin des Roziers et al. 2015). In conclusion, the de novo Thr89Ile variant was absent from control samples, and the molecular mechanism it underlies leads to the exposure of a T-antigen in a manner similar to that observed in pneumococcal hemolytic uremic syndrome. Consequently, this variant is classified as pathogenic.
OMIM	RCV003313325	SCV004012887	pathogenic	Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature	2023-07-11	no assertion criteria provided	literature only