ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.742C>T (p.Arg248Ter) (rs730881336)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211945 SCV000209680 pathogenic not provided 2016-03-16 criteria provided, single submitter clinical testing This variant is denoted ATM c.742C>T at the cDNA level and p.Arg248Ter (R248X) 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 ataxia-telangiectasia patients in the compound heterozygous state (Mitui 2005, Sasaki 1998), and in at least one breast cancer patient who also carried a BRCA2 nonsense variant (Churpek 2015). This variant is considered pathogenic.
Ambry Genetics RCV000159678 SCV000217771 pathogenic Hereditary cancer-predisposing syndrome 2018-04-02 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)
Counsyl RCV000410046 SCV000485320 likely pathogenic Ataxia-telangiectasia syndrome 2015-11-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515228 SCV000611167 pathogenic Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000410046 SCV000622747 pathogenic Ataxia-telangiectasia syndrome 2018-08-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg248*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs730881336, ExAC 0.01%). This variant has been reported in individuals affected with ataxia telangiectasia (PMID: 9711876, 16266405), prostate cancer (PMID: 27433846) and breast cancer (PMID: 26681312, 28281021). ClinVar contains an entry for this variant (Variation ID: 181913). Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.
Color RCV000159678 SCV000687770 pathogenic Hereditary cancer-predisposing syndrome 2015-04-21 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000709708 SCV000839882 pathogenic Familial cancer of breast 2017-05-24 criteria provided, single submitter clinical testing This c.742C>T (p.Arg248*) variant in the ATM gene has previously been reported in two Japanese patients with ataxia telangiectasia [PMID 9711876]. Both patients were compound heterozygous for this variant and a loss of function variant [PMID 9711876]. This c.742C>T encodes for a premature stop codon in exon 7 at amino acid position 248 of the ATM protein, leading to a loss of function of the protein. This variant has been observed in one heterozygous East Asian individual in the ExAC database (http://exac.broadinstitute.org/variant/11-108115594-C-T). It is thus classified as a pathogenic variant.

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