ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1370G>A (p.Arg457Gln)

dbSNP: rs780097986
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545001 SCV000622252 uncertain significance Ataxia-telangiectasia syndrome 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 457 of the ATM protein (p.Arg457Gln). This variant is present in population databases (rs780097986, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 453362). 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 disruptive. 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.
Ambry Genetics RCV000566779 SCV000668101 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-10 criteria provided, single submitter clinical testing The p.R457Q variant (also known as c.1370G>A), located in coding exon 9 of the ATM gene, results from a G to A substitution at nucleotide position 1370. The arginine at codon 457 is replaced by glutamine, an amino acid with highly similar properties. This alteration was observed with an allele frequency of 0.00028 in 7,051 unselected female breast cancer patients and was not observed in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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.
Mendelics RCV000545001 SCV000838487 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000761803 SCV000892000 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000566779 SCV001736246 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-12 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 457 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 been reported in individuals affected with breast cancer (PMID: 30287823). This variant has been identified in 3/251396 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.
Natera, Inc. RCV000545001 SCV001461002 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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