ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1317_1319GGA[2] (p.Glu441del) (rs377639087)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192469 SCV000249151 likely benign not specified 2015-03-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000192469 SCV000272498 likely benign not specified 2018-03-22 criteria provided, single submitter clinical testing p.Glu441del in exon 2 of TERT: This variant is classified as likely benign becau se it has been identified in 0.4% (248/68934) of European chromosomes by the Gen ome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs3776 39087). Of note, gibbons have a deletion at this position despite high nearby am ino acid conservation. In addition, although this variant has been reported in s everal studies in individuals with TERT-related conditions, many of these studie s consider the variant to be a polymorphism and the functional evidence availabl e suggests this variant does not have a significant impact on telomere length (Y amaguchi 2005, Calado 2009, Calado 2011, Kirwan 2009, Calado 2011, Fernandez 201 2, Zaug 2013, Maxwell 2016). ACMG/AMP Criteria applied: BS1; BS3_Supporting.
Invitae RCV001079649 SCV000291846 likely benign Idiopathic fibrosing alveolitis, chronic form; Dyskeratosis congenita, autosomal dominant, 2 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000370254 SCV000452691 likely benign Aplastic anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000275900 SCV000452692 likely benign Dyskeratosis Congenita, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000312359 SCV000452693 likely benign Idiopathic fibrosing alveolitis, chronic form 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000192469 SCV000565612 likely benign not specified 2016-12-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726693 SCV000702135 uncertain significance not provided 2016-10-26 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768107 SCV000899022 uncertain significance Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant, 2; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1; Cutaneous malignant melanoma 9 2018-09-12 criteria provided, single submitter clinical testing 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.
Mendelics RCV000312359 SCV001136806 benign Idiopathic fibrosing alveolitis, chronic form 2019-05-28 criteria provided, single submitter clinical testing

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