ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7421T>C (p.Leu2474Ser)

dbSNP: rs2136458920
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001359333 SCV001555196 uncertain significance Ataxia-telangiectasia syndrome 2020-04-15 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 2474 of the ATM protein (p.Leu2474Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238359 SCV002010785 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV004671365 SCV005168204 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-02 criteria provided, single submitter clinical testing The p.L2474S variant (also known as c.7421T>C), located in coding exon 49 of the ATM gene, results from a T to C substitution at nucleotide position 7421. The leucine at codon 2474 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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