ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.668A>G (p.Glu223Gly)

gnomAD frequency: 0.00003  dbSNP: rs776227830
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166516 SCV000217316 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-19 criteria provided, single submitter clinical testing The p.E223G variant (also known as c.668A>G), located in coding exon 6 of the ATM gene, results from an A to G substitution at nucleotide position 668. The glutamic acid at codon 223 is replaced by glycine, an amino acid with similar properties. This alteration was detected in a cohort of 1054 BRCA-mutation-negative Hispanic women with hereditary breast cancer (Weitzel JN et al. Cancer, 2019 Aug;125:2829-2836). This alteration was also seen in 0/732 breast cancer patients, 1/189 colorectal cancer patients and 0/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 Jan;148:285-295). This amino acid position is highly 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 RCV000539810 SCV000622685 uncertain significance Ataxia-telangiectasia syndrome 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 223 of the ATM protein (p.Glu223Gly). This variant is present in population databases (rs776227830, gnomAD 0.02%). 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: 186862). 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.
Color Diagnostics, LLC DBA Color Health RCV000166516 SCV000682360 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 223 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 hereditary cancer in the literature. This variant has been identified in 7/251080 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.
PreventionGenetics, part of Exact Sciences RCV000679139 SCV000805606 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763686 SCV000894566 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000539810 SCV001482830 uncertain significance Ataxia-telangiectasia syndrome 2019-02-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Baylor Genetics RCV003468784 SCV004208745 uncertain significance Familial cancer of breast 2024-03-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000539810 SCV002085891 uncertain significance Ataxia-telangiectasia syndrome 2020-12-18 no assertion criteria provided clinical testing

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