ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.9131dup (p.Asn3044fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822681 SCV000963491 pathogenic Ataxia-telangiectasia syndrome 2018-10-20 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the ATM gene (p.Asn3044Lysfs*19). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 13 amino acids of the ATM protein and extend the protein by an additional 6 amino acids. 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. This variant disrupts the C-terminus of the ATM protein, including a portion of the FATC domain, which spans the last 33 amino acids of the ATM protein (PMID: 19781682). An experimental study has shown that the entire FATC domain is required for ATM kinase activity in response to DNA damage (PMID: 16603769). Other variant(s) that disrupt this region (p.Arg3047*) have been determined to be pathogenic (PMID: 8755918, 19691550, 18560558,19431188). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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