ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4343T>G (p.Leu1448Ter)

dbSNP: rs1591663285
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022328 SCV001184047 pathogenic Hereditary cancer-predisposing syndrome 2019-01-15 criteria provided, single submitter clinical testing The p.L1448* pathogenic mutation (also known as c.4343T>G), located in coding exon 28 of the ATM gene, results from a T to G substitution at nucleotide position 4343. This changes the amino acid from a leucine to a stop codon within coding exon 28. 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 RCV002272388 SCV002558349 likely pathogenic not provided 2022-01-27 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 at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal history of breast cancer in published literature (Akcay 2020) and not observed in controls; This variant is associated with the following publications: (PMID: 31345636, 32658311)
Invitae RCV002551851 SCV003277438 pathogenic Ataxia-telangiectasia syndrome 2022-09-14 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: 824810). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32658311). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1448*) 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).

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