ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4741dup (p.Ile1581fs)

dbSNP: rs864622164
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543529 SCV000259526 pathogenic Ataxia-telangiectasia syndrome 2023-09-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 453535). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 24951259). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile1581Asnfs*5) 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).
Ambry Genetics RCV000561093 SCV000665183 pathogenic Hereditary cancer-predisposing syndrome 2022-04-06 criteria provided, single submitter clinical testing The c.4741dupA pathogenic mutation, located in coding exon 30 of the ATM gene, results from a duplication of A at nucleotide position 4741, causing a translational frameshift with a predicted alternate stop codon (p.I1581Nfs*5). 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.
GeneDx RCV000657386 SCV000779119 pathogenic not provided 2017-10-11 criteria provided, single submitter clinical testing This duplication of one nucleotide in ATM is denoted c.4741dupA at the cDNA level and p.Ile1581AsnfsX5 (I1581NfsX5) at the protein level. Using alternate nomenclature, this variant has previously been reported as ATM c.47356_4736insA. The normal sequence, with the base that is duplicated in brackets, is CAAAAA[dupA]TCAA. The duplication causes a frameshift which changes an Isoleucine to an Asparagine at codon 1581, and creates a premature stop codon at position 5 of the new reading frame. Although this variant has not, to our knowledge, been reported as a germline variant, it has been reported as a somatic variant in a colorectal tumor (Yu 2015). Based on current evidence, we consider this variant to be pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000561093 SCV000904614 pathogenic Hereditary cancer-predisposing syndrome 2020-04-20 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 31 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000657386 SCV001713577 likely pathogenic not provided 2020-04-17 criteria provided, single submitter clinical testing PVS1, PM2
MGZ Medical Genetics Center RCV000543529 SCV002579996 pathogenic Ataxia-telangiectasia syndrome 2021-11-04 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004023646 SCV004933459 pathogenic Familial cancer of breast 2024-01-24 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV004023646 SCV005056906 pathogenic Familial cancer of breast 2024-03-05 criteria provided, single submitter clinical testing

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.