ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8998C>T (p.Gln3000Ter) (rs587781698)

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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 RCV000129865 SCV000184682 pathogenic Hereditary cancer-predisposing syndrome 2017-06-08 criteria provided, single submitter clinical testing The p.Q3000* pathogenic mutation (also known as c.8998C>T), located in coding exon 62 of the ATM gene, results from a C to T substitution at nucleotide position 8998. This changes the amino acid from a Q to a stop codon within coding exon 62. Several protein truncating mutations associated with ataxia telangiectasia downstream of the p.Q3000* alteration have been reported in the literature (Broeks A et al. Hum. Mutat. 1998;12:330-7; Laake K et al. Hum. Mutat. 2000; 16:232-46). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl RCV000576680 SCV000678101 likely pathogenic Ataxia-telangiectasia syndrome 2017-02-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129865 SCV000687868 pathogenic Hereditary cancer-predisposing syndrome 2017-06-08 criteria provided, single submitter clinical testing
Invitae RCV000576680 SCV001408167 pathogenic Ataxia-telangiectasia syndrome 2019-09-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ATM gene (p.Gln3000*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acids of the ATM protein. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 141373). This variant disrupts the C-terminus of the ATM protein. Other variant(s) that disrupt this region (p.Arg3047*) have been determined to be pathogenic (PMID: 8755918, 19691550, 18560558, 10980530, 26628246). 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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