ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.539A>G (p.Gln180Arg)

dbSNP: rs730881334
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159675 SCV000209676 uncertain significance not provided 2014-04-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.539A>G at the cDNA level, p.Gln180Arg (Q180R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Gln180Arg 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 Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution and may affect protein integrity. ATM Gln180Arg occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether ATM Gln180Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000570786 SCV000665660 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-23 criteria provided, single submitter clinical testing The p.Q180R variant (also known as c.539A>G), located in coding exon 5 of the ATM gene, results from an A to G substitution at nucleotide position 539. The glutamine at codon 180 is replaced by arginine, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000685843 SCV000813342 uncertain significance Ataxia-telangiectasia syndrome 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 180 of the ATM protein (p.Gln180Arg). 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: 181911). 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%. 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 Diagnostics, LLC DBA Color Health RCV000570786 SCV000913531 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-15 criteria provided, single submitter clinical testing This missense variant replaces glutamine with arginine at codon 180 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000685843 SCV002094063 uncertain significance Ataxia-telangiectasia syndrome 2020-02-26 no assertion criteria provided clinical testing

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