ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3049C>T (p.Gln1017Ter) (rs730881388)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211992 SCV000209780 pathogenic not provided 2017-04-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.3049C>T at the cDNA level and p.Gln1017Ter (Q1017X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in an individual with breast cancer (Susswein 2016) and is considered pathogenic.
Ambry Genetics RCV000159761 SCV000216002 pathogenic Hereditary cancer-predisposing syndrome 2017-05-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000457084 SCV000546762 pathogenic Ataxia-telangiectasia syndrome 2018-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1017*) 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 reported in an individual affected with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 181992). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000457084 SCV000694246 pathogenic Ataxia-telangiectasia syndrome 2015-12-07 criteria provided, single submitter clinical testing Variant summary: This c.3049C>T (p.Gln1017X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein. Loss-of-function due to mutations in the ATM gene is an established disease mechanism in Ataxia-Telangiectasia (AT), a recessive disorder (ACMG, PVS1). In addition, heterozygous mutations in this gene are also associated with increased risk of breast cancer. This variant was not found in approximately120820 chromosomes from ExAC (ACMG, PM2). This variant has not been reported in affected individuals via publications. It has been reported as pathogenic by two clinical labs (ACMG, PP5). Taken together, this variant meets the ACMG criteria for classification as a Pathogenic Disease Variant. Therefore, it was classified as pathogenic.

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