ClinVar Miner

Submissions for variant NM_005157.6(ABL1):c.944C>T (p.Thr315Ile)

dbSNP: rs121913459
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV000432136 SCV002318661 likely pathogenic Chronic myelogenous leukemia, BCR-ABL1 positive 2022-03-22 criteria provided, single submitter clinical testing Same or different nucleotide change resulting in same amino acid change has been previously reported to be associated with ABL1 related disorder (ClinVar ID: VCV000012624). Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (ClinVar ID: VCV000376118). The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000432136 SCV004034968 association Chronic myelogenous leukemia, BCR-ABL1 positive 2023-09-13 criteria provided, single submitter clinical testing ABL1, a tyrosine kinase, is frequently altered by chromosomal translocations in leukemia. The BCR-ABL1 fusion is known to be oncogenic. The ABL1 T315I is a known resistance mutation. Diagnostic Summary: The presence of a BCR-ABL1 fusion is consistent with the diagnosis of chronic myeloid leukemia. Therapeutic Summary: The presence of the BCR-ABL1 fusion in myeloproliferative neoplasms is diagnostic of chronic myelogenous leukemia (CML). The NCCN considers the ABL1 T315I mutation as "contraindicated" for the therapies imatinib, dasatinib, nilotinib, and bosutinib in patients with BCR-ABL1 positive (+) CML. The multikinase inhibitor ponatinib and the BCR-ABL1 inhibitor asciminib are FDA approved for adult patients with ABL1 T315I+ BCRABL1 fusion+ CML.
OMIM RCV000013459 SCV000033706 pathogenic Leukemia, Philadelphia chromosome-positive, resistant to imatinib 2015-03-05 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432136 SCV000505087 likely pathogenic Chronic myelogenous leukemia, BCR-ABL1 positive 2016-03-10 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442565 SCV000505088 likely pathogenic Lymphoblastic leukemia, acute, with lymphomatous features 2015-07-14 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.