ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5573G>A (p.Trp1858Ter) (rs879254076)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236378 SCV000293377 pathogenic not provided 2017-01-16 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.5573G>A at the cDNA level and p.Trp1858Ter (W1858X) 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. Although this variant has not, to our knowledge, been reported in the literature, the adjacent variant c.5574G>A, which also results in a premature stop codon at this residue (p.Trp1858Ter) has been reported in the compound heterozygous state with another ATM pathogenic variant in an individual with Ataxia-telangiectasia (Delia 2000). We therefore consider ATM c.5573G>A to be pathogenic.
Invitae RCV000628037 SCV000748925 pathogenic Ataxia-telangiectasia syndrome 2019-12-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1858*) 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 not been reported in the literature in individuals with ATM-related disease. However, a different nucleotide change leading to the same protein effect (p.Trp1858*) has been reported in the compound heterozygous state in a patient affected with ataxia-telangiectasia (PMID: 10864201). ClinVar contains an entry for this variant (Variation ID: 246068). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000628037 SCV000790919 likely pathogenic Ataxia-telangiectasia syndrome 2017-04-14 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000628037 SCV001150022 pathogenic Ataxia-telangiectasia syndrome 2019-06-13 criteria provided, single submitter clinical testing

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