ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4378G>T (p.Ala1460Ser)

dbSNP: rs1060501675
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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 RCV000477246 SCV000547062 uncertain significance Ataxia-telangiectasia syndrome 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1460 of the ATM protein (p.Ala1460Ser). This variant is not present in population databases (gnomAD no frequency). 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: 407677). 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.
Ambry Genetics RCV001022386 SCV001184115 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-29 criteria provided, single submitter clinical testing The p.A1460S variant (also known as c.4378G>T), located in coding exon 28 of the ATM gene, results from a G to T substitution at nucleotide position 4378. The alanine at codon 1460 is replaced by serine, an amino acid with similar properties. 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.
Color Diagnostics, LLC DBA Color Health RCV001022386 SCV001734191 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-23 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 1460 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 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 RCV003470436 SCV004210303 uncertain significance Familial cancer of breast 2024-02-09 criteria provided, single submitter clinical testing

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