ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3669_3670insTAG (p.Leu1224Ter)

dbSNP: rs2082301397
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001201849 SCV001372940 pathogenic Ataxia-telangiectasia syndrome 2023-05-22 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: 933605). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1224*) 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 RCV003284038 SCV004007284 pathogenic Hereditary cancer-predisposing syndrome 2023-05-16 criteria provided, single submitter clinical testing The c.3669_3670insTAG pathogenic mutation (also known as p.L1224*), located in coding exon 24 of the ATM gene, results from an in-frame TAG insertion at nucleotide positions 3669 to 3670. This changes the amino acid from a leucine to a stop codon within coding exon 24. This mutation was identified in an individual with cholangiocarcinoma diagnosed at age 36 (Maynard H et al. Cancer, 2020 Jan;126:1995-2002). 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-mediatedmRNAdecay.As such, this alteration is interpreted as a disease-causing mutation.

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