ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3894dup (p.Ala1299fs) (rs587781823)

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
Ambry Genetics RCV000130103 SCV000184933 pathogenic Hereditary cancer-predisposing syndrome 2019-05-23 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000231882 SCV000282945 pathogenic Ataxia-telangiectasia syndrome 2019-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala1299Cysfs*3) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with ataxia-telangiectasia (PMID: 10330348, 12815592, 19691550). This variant is also known as c.3894_3895insT in the literature.ClinVar contains an entry for this variant (Variation ID: 141534). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000342511 SCV000329805 pathogenic not provided 2017-06-27 criteria provided, single submitter clinical testing This duplication of one nucleotide in ATM is denoted c.3894dupT at the cDNA level and p.Ala1299CysfsX3 (A1299CfsX3) at the protein level. The normal sequence, with the base that is duplicated in braces, is ATTT[T]GCCT. The duplication causes a frameshift, which changes an Alanine to a Cysteine at codon 1299, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.3894dupT, also known as ATM 3894insT and c.3894_3895insT, has been observed in the homozygous and compound heterozygous states in individuals with ataxia-telangiectasia (Teraoka 1999, Mitui 2003, Chessa 2009). Based on currently available evidence, we consider this variant to be pathogenic.
Color RCV000130103 SCV000905172 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000231882 SCV000918564 pathogenic Ataxia-telangiectasia syndrome 2018-09-14 criteria provided, single submitter clinical testing Variant summary: ATM c.3894dupT (p.Ala1299CysfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.1e-06 in 246054 control chromosomes (gnomAD). c.3894dupT has been reported in the literature in multiple individuals affected with Ataxia-Telangiectasia (Chessa_2009, Micol_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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.