ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.378del (p.Asp126fs) (rs587781449)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129372 SCV000184136 pathogenic Hereditary cancer-predisposing syndrome 2019-05-08 criteria provided, single submitter clinical testing The c.378delT pathogenic mutation, located in coding exon 4 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 378, causing a translational frameshift with a predicted alternate stop codon (p.D126Efs*3). This mutation has been identified in a patient with bilateral breast cancer (Crawford B et al. Breast Cancer Res. Treat. 2017 Jun;163:383-390). 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 RCV000464543 SCV000546723 pathogenic Ataxia-telangiectasia syndrome 2018-03-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp126Glufs*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 not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 141037). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000129372 SCV000682160 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
GeneDx RCV000657371 SCV000779104 pathogenic not provided 2017-08-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.378delT at the cDNA level and p.Asp126GlufsX3 (D126EfsX3) at the protein level. The normal sequence, with the base that is deleted in brackets, is TGGA[delT]ACAG. The deletion causes a frameshift which changes an Aspartic Acid to a Glutamic Acid at codon 126, 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.378delT has been observed in a woman with bilateral breast cancer (Crawford 2017). We consider this variant to be pathogenic.
Counsyl RCV000464543 SCV000790486 likely pathogenic Ataxia-telangiectasia syndrome 2017-04-03 criteria provided, single submitter clinical testing

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