ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4466G>T (p.Arg1489Leu)

dbSNP: rs201594549
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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 RCV001051654 SCV001215822 uncertain significance Ataxia-telangiectasia syndrome 2023-07-07 criteria provided, single submitter clinical testing 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 847998). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs201594549, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1489 of the ATM protein (p.Arg1489Leu). 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 RCV001182962 SCV001348591 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-25 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 1489 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251278 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.
Sema4, Sema4 RCV001182962 SCV002534823 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-16 criteria provided, single submitter curation
Ambry Genetics RCV001182962 SCV002638469 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-07 criteria provided, single submitter clinical testing The p.R1489L variant (also known as c.4466G>T), located in coding exon 29 of the ATM gene, results from a G to T substitution at nucleotide position 4466. The arginine at codon 1489 is replaced by leucine, 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.

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