ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1774A>G (p.Ser592Gly)

dbSNP: rs1060501558
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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 RCV000466164 SCV000546720 uncertain significance Ataxia-telangiectasia syndrome 2021-08-03 criteria provided, single submitter clinical testing In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. This sequence change replaces serine with glycine at codon 592 of the ATM protein (p.Ser592Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine.
Ambry Genetics RCV002411450 SCV002716875 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-08 criteria provided, single submitter clinical testing The p.S592G variant (also known as c.1774A>G), located in coding exon 10 of the ATM gene, results from an A to G substitution at nucleotide position 1774. The serine at codon 592 is replaced by glycine, an amino acid with similar properties. This amino acid position is not 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.
Color Diagnostics, LLC DBA Color Health RCV002411450 SCV004359755 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-07 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 592 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 ATM-related disorders 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 RCV004567990 SCV005057008 uncertain significance Familial cancer of breast 2024-02-07 criteria provided, single submitter clinical testing

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