ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1080T>G (p.Asp360Glu)

gnomAD frequency: 0.00001  dbSNP: rs199869975
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159682 SCV000209685 uncertain significance not provided 2014-09-11 criteria provided, single submitter clinical testing This variant is denoted ATM c.1080T>G at the cDNA level, p.Asp360Glu (D360E) at the protein level, and results in the change of an Aspartic Acid to a Glutamic Acid (GAT>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asp360Glu 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 Aspartic Acid and Glutamic Acid share similar properties, this is considered a conservative amino acid substitution. ATM Asp360Glu occurs at a position that is moderately conserved across mammals 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 Asp360Glu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565732 SCV000660498 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-13 criteria provided, single submitter clinical testing The p.D360E variant (also known as c.1080T>G), located in coding exon 8 of the ATM gene, results from a T to G substitution at nucleotide position 1080. The aspartic acid at codon 360 is replaced by glutamic acid, 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 RCV000696558 SCV000825122 uncertain significance Ataxia-telangiectasia syndrome 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 360 of the ATM protein (p.Asp360Glu). This variant is present in population databases (rs199869975, gnomAD 0.003%). 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: 181917). 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.
Color Diagnostics, LLC DBA Color Health RCV000565732 SCV000904437 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 360 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 been identified in 1/250194 chromosomes 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243828 SCV002512197 uncertain significance Familial cancer of breast 2021-11-01 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderate, BP4 supporting
Baylor Genetics RCV002243828 SCV004209533 uncertain significance Familial cancer of breast 2023-08-30 criteria provided, single submitter clinical testing
Natera, Inc. RCV000696558 SCV001456879 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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