ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.412G>A (p.Gly138Arg)

gnomAD frequency: 0.00001  dbSNP: rs150661813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000627866 SCV000748750 uncertain significance Ataxia-telangiectasia syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 138 of the ATM protein (p.Gly138Arg). This variant is present in population databases (rs150661813, gnomAD 0.006%). 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: 524242). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001021921 SCV001183598 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-18 criteria provided, single submitter clinical testing The p.G138R variant (also known as c.412G>A), located in coding exon 4 of the ATM gene, results from a G to A substitution at nucleotide position 412. The glycine at codon 138 is replaced by arginine, an amino acid with dissimilar 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.
Color Diagnostics, LLC DBA Color Health RCV001021921 SCV001345924 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-17 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 138 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 3/251314 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. RCV000627866 SCV002090889 uncertain significance Ataxia-telangiectasia syndrome 2019-10-28 no assertion criteria provided clinical testing

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