ClinVar

Description

TERT NM_198253.2 exon 2 p.Glu441del (c.1323_1325del): This variant has been reported in the literature as heterozygous in at 2 least individuals with varying phenotypes (hepatic cirrhosis, aplastic anemia) as well as homozygous in 1 individual with acute myelogenous leukemia (AML) (Yamaguchi 2005 PMID:15814878, Calado 2009 PMID:19674077, Calado 2009 PMID:19147845, Calado 2011 PMIDL21520173). The interpretation of this variant in the current literature is unclear, with at least 2 publications calling this variant a polymorphism (Yamaguchi 2005 PMID:15814878, Maxwell 2016 PMID:27153395). Functional studies are also conflicting, suggesting either a 40% reduction (compared to WT) to near normal effect of this variant on telomerase enzyme activity (Calado 2009 PMID:19147845, Zaug 2013 PMID:23901009). This variant is also present in 0.3% (248/68934) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/5-1293675-GTCC-G). This variant is present in ClinVar, with discrepant classifications ranging from likely benign to variant of uncertain significance (Variation ID:212398).This variant represents an in-frame deletion of 1 glutamic acid residue in a repeat of 3 glutamic acids. This is not predicted to alter the reading frame, but the ultimate effect of this variant on the protein is unclear. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.