ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7897T>G (p.Leu2633Val)

gnomAD frequency: 0.00001  dbSNP: rs587779868
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115257 SCV000149166 uncertain significance not provided 2013-10-09 criteria provided, single submitter clinical testing This variant is denoted c.7897T>G at the cDNA level or p.Leu2633Val (L2633V) at the protein level. This variant results in the replacement of a Leucine codon (TTA) with a Valine codon (GTA) at amino acid position 2633 of the ATM gene. The Leu2633Val missense substitution has not been published as a mutation, nor has it been reported as a polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports Leu2633Val was not observed in approximately 6500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. The Leu2633Val variant is a conservative substitution as a neutral Leucine residue is replaced by a neutral Valine residue at a position that is evolutionarily moderately conserved across species and is not located in a known functional domain. Additionally, in silico models are consistent in their prediction of a benign effect on protein structure and function. Based on the currently available information, we consider Leu2633Val to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000475783 SCV000546707 uncertain significance Ataxia-telangiectasia syndrome 2023-08-24 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 127451). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2633 of the ATM protein (p.Leu2633Val).
Ambry Genetics RCV002415591 SCV002681077 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-16 criteria provided, single submitter clinical testing The p.L2633V variant (also known as c.7897T>G), located in coding exon 52 of the ATM gene, results from a T to G substitution at nucleotide position 7897. The leucine at codon 2633 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000115257 SCV002774795 uncertain significance not provided 2021-08-10 criteria provided, single submitter clinical testing

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