ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4735C>T (p.Gln1579Ter) (rs869312755)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210197 SCV000273529 pathogenic Hereditary cancer-predisposing syndrome 2017-10-17 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)
Baylor Genetics RCV000234068 SCV000807210 pathogenic Ataxia-telangiectasia syndrome 2017-09-01 criteria provided, single submitter clinical testing This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found twice in our laboratory in trans with a deleterious frameshift mutation in a set of affected siblings. 9-year-old female & 12-year-old male sibs had cerebellar ataxia, oculomotor apraxia, intellectual disability, hypertonia, spasticity, peripheral neuropathy, pigmentary skin changes.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000255389 SCV000692733 likely pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing
Color RCV000210197 SCV000913947 pathogenic Hereditary cancer-predisposing syndrome 2018-07-16 criteria provided, single submitter clinical testing
Counsyl RCV000234068 SCV000678088 likely pathogenic Ataxia-telangiectasia syndrome 2016-12-14 criteria provided, single submitter clinical testing
GeneDx RCV000255389 SCV000322058 pathogenic not provided 2017-08-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.4735C>T at the cDNA level and p.Gln1579Ter (Q1579X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the compound heterozygous state with a second ATM pathogenic variant in at least one individual with ataxia telangiectasia (R?be 2010, Hoche 2014), and in a woman with breast cancer and a family history of ovarian cancer (Shirts 2016). We consider this variant to be pathogenic.
Invitae RCV000234068 SCV000282966 pathogenic Ataxia-telangiectasia syndrome 2016-06-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1579 (p.Gln1579*) of the ATM gene. It is expected to result in an absent or disrupted protein product. Truncating variants in ATM are known to be pathogenic. This particular truncation has been reported in the literature in an individual affected with breast cancer (PMID: 26845104) and in an individual affected with ataxia telangiectasia (PMID: 25037873). For these reasons, this variant has been classified as Pathogenic.
University of Washington Department of Laboratory Medicine,University of Washington RCV000210197 SCV000266017 likely pathogenic Hereditary cancer-predisposing syndrome 2015-11-20 criteria provided, single submitter clinical testing

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