ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5798G>A (p.Trp1933Ter) (rs876658740)

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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 RCV000218884 SCV000274398 pathogenic Hereditary cancer-predisposing syndrome 2017-05-03 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 RCV000409971 SCV000486860 likely pathogenic Ataxia-telangiectasia syndrome 2016-08-24 criteria provided, single submitter clinical testing
GeneDx RCV000627198 SCV000748182 pathogenic not provided 2018-12-21 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.5798G>A at the cDNA level and p.Trp1933Ter (W1933X) 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. This variant has been observed in an individual with a personal and family history of early-onset breast cancer (Meiss 2018) and is considered pathogenic.
Invitae RCV000409971 SCV000833572 pathogenic Ataxia-telangiectasia syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1933*) 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. ClinVar contains an entry for this variant (Variation ID: 230743). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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