ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3880dup (p.Ile1294fs) (rs1057516541)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410605 SCV000485847 likely pathogenic Ataxia-telangiectasia syndrome 2016-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569268 SCV000668150 pathogenic Hereditary cancer-predisposing syndrome 2017-08-11 criteria provided, single submitter clinical testing The c.3880dupA pathogenic mutation, located in coding exon 25 of the ATM gene, results from a duplication of A at nucleotide position 3880, causing a translational frameshift with a predicted alternate stop codon (p.I1294Nfs*8). This mutation (designated as c.3880insA) was reported in conjunction with another truncating ATM mutation in a patient with ataxia-telangiectasia. Cell lines derived from this individual demonstrated absence of ATM protein expression (Keimling M et al. FASEB J. 2011 Nov;25(11):3849-60). In addition to the clinical data presented in the literature, 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.
Invitae RCV000410605 SCV000937930 pathogenic Ataxia-telangiectasia syndrome 2020-07-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile1294Asnfs*8) 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 combination with another ATM variant in an individual affected with ataxia telangiectasia (PMID: 21778326). This variant is also known as c.3880fs in the literature. ClinVar contains an entry for this variant (Variation ID: 370505). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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