ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4396C>T (p.Arg1466Ter) (rs730881369)

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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 RCV000445657 SCV000581466 pathogenic Hereditary cancer-predisposing syndrome 2017-12-11 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)
Color RCV000445657 SCV000537651 pathogenic Hereditary cancer-predisposing syndrome 2015-01-23 criteria provided, single submitter clinical testing
Counsyl RCV000227538 SCV000795828 pathogenic Ataxia-telangiectasia syndrome 2017-11-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762821 SCV000893179 pathogenic Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000657608 SCV000779350 pathogenic not provided 2018-02-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.4396C>T at the cDNA level and p.Arg1466Ter (R1466X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), 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 homozygous or compound heterozygous state in several individuals with Ataxia-telangiectasia and in the heterozygous state in at least one individual with familial breast cancer (Chessa 2009, Snape 2012, Chen 2015). Based on current evidence, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000227538 SCV000694281 pathogenic Ataxia-telangiectasia syndrome 2016-01-22 criteria provided, single submitter clinical testing
Invitae RCV000227538 SCV000282958 pathogenic Ataxia-telangiectasia syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1466 (p.Arg1466*) of the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs730881369, ExAC 0.006%). This variant has been reported in many individuals affected with ataxia-telangiectasia (PMID: 10425038, 12552559, 19691550, 22213089, 22527104, 26439923). ClinVar contains an entry for this variant (Variation ID: 236716). Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000227538 SCV000838539 pathogenic Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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