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Gene | ATM |
Variant | S49C |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ATM S49C does not lie within any known functional domains of the Atm protein (UniProt.org). S49C retains the ability to induce expression of TP53 target genes upon DNA damage in patient-derived cells in culture (PMID: 23585524), results in similar cell survival upon treatment with DNA damaging agents to wild-type Atm, and retains the ability to phosphorylate some Atm targets, but leads to decreased phosphorylation of the Atm target CDC25A, and decreased HDR activity in cultured cells (PMID: 35354106), and therefore, its effect on Atm protein function is unknown. |
Associated Drug Resistance | |
Category Variants Paths |
ATM mutant ATM S49C |
Transcript | NM_000051.4 |
gDNA | chr11:g.108227849C>G |
cDNA | c.146C>G |
Protein | p.S49C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011542842.3 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542840.4 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017792.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426979.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017790 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017791.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426975.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_006718843.4 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_006718843 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017789 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542843 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542842.4 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017792 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_005271562 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_000051.3 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542843.3 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426981.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542843.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351836.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542842 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_000051 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_006718843.5 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_000051.4 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017791 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351834.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351835.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_005271562.5 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542840 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_011542840.3 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017789.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017790.3 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_005271561 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426977.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_005271562.6 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351836.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_017017790.2 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351834.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426978.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
XM_047426976.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
NM_001351835.1 | chr11:g.108227849C>G | c.146C>G | p.S49C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ATM mutant | mantle cell lymphoma | predicted - sensitive | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). | 30455436 |
ATM mutant | breast cancer | no benefit | Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 4 patients with metastatic breast cancer harboring only germline mutations in ATM (PMID: 33119476; NCT03344965). | 33119476 |
ATM mutant | ovarian cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing ovarian cancer (NCCN.org). | detail... |
ATM mutant | Advanced Solid Tumor | conflicting | Olaparib | Phase II | Actionable | In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938). | detail... |
ATM mutant | Advanced Solid Tumor | conflicting | Olaparib | Phase II | Actionable | In a Phase II trial (TAPUR), Lynparza (olaparib) treatment resulted in an objective response rate of 8% and a disease control rate of 25% (9/36, 1 complete response, 2 partial responses, 6 stable disease at 16+ weeks) in patients with advanced solid tumors harboring ATM mutations (Cancer Res 2022;82(12_Suppl):Abstract nr CT110; NCT02693535). | detail... |
ATM mutant | pancreatic cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing pancreatic cancer (NCCN.org). | detail... |
ATM mutant | prostate cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org). | detail... |
ATM mutant | lung non-small cell carcinoma | predicted - sensitive | M1774 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, M1774 inhibited tumor growth in a cell line xenograft model of non-small cell lung cancer harboring an ATM mutation (PMID: 38407317). | 38407317 |
ATM mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing breast cancer (NCCN.org). | detail... |
ATM mutant | prostate cancer | sensitive | Olaparib | Phase II | Actionable | In a Phase II clinical trial, 80% (4/5) of metastatic castration-resistant prostate cancer patients with ATM truncation mutations demonstrated response to Lynparza (olaparib) treatment (Cancer Res August 1, 2015 75:CT322). | detail... |