ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3381_3384del (p.Gln1128fs)

dbSNP: rs587781971
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130359 SCV000185210 pathogenic Hereditary cancer-predisposing syndrome 2024-08-13 criteria provided, single submitter clinical testing The c.3381_3384delTCAG pathogenic mutation, located in coding exon 22 of the ATM gene, results from a deletion of 4 nucleotides at nucleotide positions 3381 to 3384, causing a translational frameshift with a predicted alternate stop codon (p.Q1128Kfs*3). This pathogenic mutation (designated as 3381delTCAG) was reported in an individual with ataxia-telangiectasia, although it was not noted whether a second mutation was identified (Castellví-Bel S et al. Hum. Mutat. 1999; 14(2):156-62). This mutation was also observed in conjunction with a BRCA2 pathogenic mutation in an individual diagnosed with breast cancer at age 33 who had a family history of breast, pancreatic, thyroid and esophageal cancer (Tung N et al. J. Clin. Oncol. 2016 May; 34(13):1460-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000410669 SCV000622416 pathogenic Ataxia-telangiectasia syndrome 2024-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1128Lysfs*3) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 10425038). This variant is also known as 3381delTCAG. ClinVar contains an entry for this variant (Variation ID: 141734). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000130359 SCV000911666 pathogenic Hereditary cancer-predisposing syndrome 2023-03-28 criteria provided, single submitter clinical testing This variant, also referred to as '3381delTCAG', deletes 4 nucleotides in exon 23 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in an individual affected with ataxia telangiectasia, however, the report did not mention a second mutation (PMID: 10425038). This variant was reported in an individual diagnosed with breast cancer at 33 years old who carried a second pathogenic variant in BRCA2 (PMID: 26976419) and an individual affected with prostate cancer (DOI: 10.1097/JU.0000000000003186). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
GeneDx RCV001778751 SCV002015598 pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in an individual with a personal history of breast cancer and family history of breast, pancreatic, and other cancers who also harbored a pathogenic BRCA2 variant (Tung et al., 2016); Identified in an individual with ataxia telangiectasia for whom clinical and other testing details are limited (Castellvi-Bel et al., 1999); This variant is associated with the following publications: (PMID: 28152038, 27304073, 26976419, 23807571, 25614872, 36974724, 30625039, 10425038)
Sema4, Sema4 RCV000130359 SCV002535946 likely pathogenic Hereditary cancer-predisposing syndrome 2021-05-25 criteria provided, single submitter curation
Revvity Omics, Revvity RCV000410669 SCV003811123 pathogenic Ataxia-telangiectasia syndrome 2022-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003467144 SCV004210267 pathogenic Familial cancer of breast 2023-06-20 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003467144 SCV004931280 pathogenic Familial cancer of breast 2024-01-22 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Counsyl RCV000410669 SCV000486571 likely pathogenic Ataxia-telangiectasia syndrome 2016-06-27 no assertion criteria provided clinical testing This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

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