ClinVar Miner

Submissions for variant NM_001351834.2(ATM):c.1288_1289TG[1] (p.Cys430_Glu431delinsTer) (rs587781598)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129663 SCV000184461 pathogenic Hereditary cancer-predisposing syndrome 2018-02-16 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
GeneDx RCV000236686 SCV000292788 pathogenic not provided 2018-08-20 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted ATM c.1290_1291delTG at the cDNA level and p.Cys430Ter (C430X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACTG[delTG]AGCT. The deletion creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.1290_1291delTG, also published as 1287delTG using alternate nomenclature, has been reported in individuals with ataxia telangiectasia (A-T) as well as in at least two individuals with breast cancer (Stankovic 1998, Li 2000, Worth 2013, Decker 2017). We consider this variant to be pathogenic.
Counsyl RCV000410187 SCV000485526 likely pathogenic Ataxia-telangiectasia syndrome 2015-12-28 criteria provided, single submitter clinical testing
Invitae RCV000410187 SCV000547149 pathogenic Ataxia-telangiectasia syndrome 2019-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys430*) 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 observed in two individuals with ataxia-telangiectasia (PMID: 9463314, 23143971). ClinVar contains an entry for this variant (Variation ID: 141241). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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