ClinVar Miner

Submissions for variant NM_001330368.2(C11orf65):c.640+20583_640+20584del (rs876660022)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222939 SCV000277087 pathogenic Hereditary cancer-predisposing syndrome 2018-11-29 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
Invitae RCV000814547 SCV000954960 pathogenic Ataxia-telangiectasia syndrome 2018-07-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ATM gene (p.Ser3001Phefs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acids of the ATM protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in individuals affected with ataxia telangectasia (PMID: 8845835, 9792409). This variant is also known as c.9001delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 232841). This frameshift variant is expected to disrupt the C-terminal FATC domain (residues 2963-3056 or 3024-3056) of the ATM protein, which is required for binding to TIP60 for signaling activation (PMID: 23532176, 19781682, 18813293). A downstream truncating variant (p.Arg3047*) affecting the same region has been determined to be pathogenic (PMID: 8755918, 19691550, 18560558, 10980530, 26628246). This suggests that disruption of this region of the ATM protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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