ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2225A>C (p.Lys742Thr)

dbSNP: rs2135394428
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001593776 SCV001816930 uncertain significance not provided 2020-02-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882724 SCV002156000 uncertain significance Ataxia-telangiectasia syndrome 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 742 of the ATM protein (p.Lys742Thr). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002425007 SCV002727531 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-24 criteria provided, single submitter clinical testing The p.K742T variant (also known as c.2225A>C), located in coding exon 13 of the ATM gene, results from an A to C substitution at nucleotide position 2225. The lysine at codon 742 is replaced by threonine, an amino acid with similar properties. This amino acid position is 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.

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