ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4480T>C (p.Cys1494Arg)

dbSNP: rs1060501576
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000458675 SCV000546776 uncertain significance Ataxia-telangiectasia syndrome 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1494 of the ATM protein (p.Cys1494Arg). 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: 407519). 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 RCV000570310 SCV000660579 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-17 criteria provided, single submitter clinical testing The p.C1494R variant (also known as c.4480T>C), located in coding exon 29 of the ATM gene, results from a T to C substitution at nucleotide position 4480. The cysteine at codon 1494 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001764394 SCV001999443 uncertain significance not provided 2019-10-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004551521 SCV004120851 uncertain significance ATM-related disorder 2023-02-07 criteria provided, single submitter clinical testing The ATM c.4480T>C variant is predicted to result in the amino acid substitution p.Cys1494Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant has been interpreted as uncertain (ncbi.nlm.nih.gov/clinvar/variation/407519/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Color Diagnostics, LLC DBA Color Health RCV000570310 SCV004360984 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-21 criteria provided, single submitter clinical testing This missense variant replaces cysteine with arginine at codon 1494 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.
Baylor Genetics RCV004567991 SCV005056926 uncertain significance Familial cancer of breast 2024-03-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000458675 SCV001462147 uncertain significance Ataxia-telangiectasia syndrome 2020-04-17 no assertion criteria provided clinical testing

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