ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4087A>G (p.Thr1363Ala) (rs587779837)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115186 SCV000149095 uncertain significance not provided 2014-01-16 criteria provided, single submitter clinical testing This variant is denoted ATM c.4087A>G at the cDNA level, p.Thr1363Ala (T1363A) at the protein level, and results in the change of a Threonine to an Alanine (ACT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Thr1363Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a neutral polar amino acid is replaced with a neutral non-polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider ATM Thr1363Ala to be a variant of uncertain significance.
Ambry Genetics RCV000574275 SCV000667928 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-05 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000628153 SCV000749046 uncertain significance Ataxia-telangiectasia syndrome 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1363 of the ATM protein (p.Thr1363Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs587779837, ExAC 0.002%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127381). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000574275 SCV000904609 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-21 criteria provided, single submitter clinical testing

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