ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3725C>G (p.Thr1242Arg)

dbSNP: rs1266811647
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572908 SCV000665274 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-03 criteria provided, single submitter clinical testing The p.T1242R variant (also known as c.3725C>G), located in coding exon 24 of the ATM gene, results from a C to G substitution at nucleotide position 3725. The threonine at codon 1242 is replaced by arginine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000700441 SCV000829195 uncertain significance Ataxia-telangiectasia syndrome 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 1242 of the ATM protein (p.Thr1242Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 481111). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.
Natera, Inc. RCV000700441 SCV002079014 uncertain significance Ataxia-telangiectasia syndrome 2021-02-08 no assertion criteria provided clinical testing

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