ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4370T>G (p.Leu1457Ter) (rs373226793)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131174 SCV000186120 pathogenic Hereditary cancer-predisposing syndrome 2019-07-30 criteria provided, single submitter clinical testing The p.L1457* pathogenic mutation (also known as c.4370T>G), located in coding exon 28 of the ATM gene, results from a T to G substitution at nucleotide position 4370. This changes the amino acid from a leucine to a stop codon within coding exon 28. This mutation was identified in 1/102 high risk patients with prostate cancer (Pilié PG et al. Cancer, 2017 Oct;123:3925-3932). 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.
Counsyl RCV000411522 SCV000487090 likely pathogenic Ataxia-telangiectasia syndrome 2016-10-05 criteria provided, single submitter clinical testing
Invitae RCV000411522 SCV001199386 pathogenic Ataxia-telangiectasia syndrome 2019-09-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1457*) 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 an individual affected with prostate cancer (PMID: 28657667). ClinVar contains an entry for this variant (Variation ID: 142188). 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 RCV001560591 SCV001783031 likely pathogenic not provided 2021-01-07 criteria provided, single submitter clinical testing Nonsense 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 in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 28657667, 24763289)

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