ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.9071C>T (p.Thr3024Ile)

gnomAD frequency: 0.00001  dbSNP: rs786203183
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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 RCV000166387 SCV000217179 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-25 criteria provided, single submitter clinical testing The p.T3024I variant (also known as c.9071C>T), located in coding exon 62 of the ATM gene, results from a C to T substitution at nucleotide position 9071. The threonine at codon 3024 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000481586 SCV000568041 uncertain significance not provided 2015-09-27 criteria provided, single submitter clinical testing This variant is denoted ATM c.9071C>T at the cDNA level, p.Thr3024Ile (T3024I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACT>ATT). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. ATM Thr3024Ile 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. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Thr3024Ile occurs at a position that is conserved in mammals and is located in the FATC domain (Stracker 2013, Tavtigian 2009). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Thr3024Ile is pathogenic or benign.
Color Diagnostics, LLC DBA Color Health RCV000166387 SCV000905062 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001053518 SCV001217785 uncertain significance Ataxia-telangiectasia syndrome 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 3024 of the ATM protein (p.Thr3024Ile). 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: 186742). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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