ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3679A>G (p.Thr1227Ala)

gnomAD frequency: 0.00001  dbSNP: rs1047871047
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000468295 SCV000546726 uncertain significance Ataxia-telangiectasia syndrome 2024-02-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1227 of the ATM protein (p.Thr1227Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 407491). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002481421 SCV002774781 uncertain significance not provided 2021-06-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV004022642 SCV005038164 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-17 criteria provided, single submitter clinical testing The p.T1227A variant (also known as c.3679A>G), located in coding exon 24 of the ATM gene, results from an A to G substitution at nucleotide position 3679. The threonine at codon 1227 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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