ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4055A>G (p.His1352Arg)

gnomAD frequency: 0.00001  dbSNP: rs925124248
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568405 SCV000660673 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-17 criteria provided, single submitter clinical testing The p.H1352R variant (also known as c.4055A>G), located in coding exon 26 of the ATM gene, results from an A to G substitution at nucleotide position 4055. The histidine at codon 1352 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001235770 SCV001408475 uncertain significance Ataxia-telangiectasia syndrome 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1352 of the ATM protein (p.His1352Arg). 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: 479028). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV003114681 SCV003798702 uncertain significance not provided 2023-02-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003470807 SCV004207484 uncertain significance Familial cancer of breast 2023-10-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV001235770 SCV002079114 uncertain significance Ataxia-telangiectasia syndrome 2020-07-13 no assertion criteria provided clinical testing

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