ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1675A>G (p.Ile559Val)

gnomAD frequency: 0.00001  dbSNP: rs1060501545
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469013 SCV000546689 uncertain significance Ataxia-telangiectasia syndrome 2022-09-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 407476). This variant has not been reported in the literature in individuals affected with ATM-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 559 of the ATM protein (p.Ile559Val).
Color Diagnostics, LLC DBA Color Health RCV000776544 SCV000912147 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 559 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798833 SCV002043243 uncertain significance Breast and/or ovarian cancer 2020-06-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000776544 SCV005168314 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-22 criteria provided, single submitter clinical testing The p.I559V variant (also known as c.1675A>G), located in coding exon 10 of the ATM gene, results from an A to G substitution at nucleotide position 1675. The isoleucine at codon 559 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000469013 SCV002083713 uncertain significance Ataxia-telangiectasia syndrome 2020-07-10 no assertion criteria provided clinical testing

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