ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.170G>A (p.Trp57Ter) (rs587779818)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115145 SCV000186179 pathogenic Hereditary cancer-predisposing syndrome 2017-07-19 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)
Blueprint Genetics RCV000211942 SCV000927698 pathogenic not provided 2018-05-21 criteria provided, single submitter clinical testing
Color RCV000115145 SCV000292162 pathogenic Hereditary cancer-predisposing syndrome 2015-06-17 criteria provided, single submitter clinical testing
Counsyl RCV000197540 SCV000487229 pathogenic Ataxia-telangiectasia syndrome 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000211942 SCV000149054 pathogenic not provided 2018-01-05 criteria provided, single submitter clinical testing This variant is denoted ATM c.170G>A at the cDNA level and p.Trp57Ter (W57X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), 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 association with recessively-inherited Ataxia Telangiectasia (Li 2000). More recently, ATM Trp57Ter has been observed in several individuals, including at least two with breast cancer, one with colon cancer, one with sessile serrated polyposis, and four with pancreatic cancer (Tavtigian 2009, Goldgar 2011, Roberts 2012, Gala 2014, Susswein 2015, Seifert 2016, Bunnell 2017). Based on currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000197540 SCV000253737 pathogenic Ataxia-telangiectasia syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp57*) 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 individuals affected with ataxia-telangiectasia, breast cancer, multiple sessile serrated adenomas, colon cancer, and pancreatic cancer (PMID: 10817650, 21787400, 24512911, 26681312, 27083775). It also segregated with pancreatic cancer in a single family (PMID: 22585167). ClinVar contains an entry for this variant (Variation ID: 127341). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics RCV000211942 SCV000805503 pathogenic not provided 2017-06-12 criteria provided, single submitter clinical testing

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