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 2018-07-02 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000457084 SCV000546762 pathogenic Ataxia-telangiectasia syndrome 2019-11-15 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 2019-10-28 criteria provided, single submitter clinical testing Variant summary: ATM c.3049C>T (p.Gln1017X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3085dupA (p.Thr1029fsX19), c.3245_3247delinsTGAT (p.His1082fsX14), c.3372C>G (p.Tyr1124X)). The variant was absent in 251048 control chromosomes (gnomAD). c.3049C>T has been reported in the literature in an individual affected with Breast Cancer (Susswein_2016).To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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