ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5827A>G (p.Lys1943Glu)

gnomAD frequency: 0.00001  dbSNP: rs779692309
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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 RCV001058829 SCV001223425 uncertain significance Ataxia-telangiectasia syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 1943 of the ATM protein (p.Lys1943Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs779692309, ExAC 0.003%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002355058 SCV002650798 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-03 criteria provided, single submitter clinical testing The p.K1943E variant (also known as c.5827A>G), located in coding exon 38 of the ATM gene, results from an A to G substitution at nucleotide position 5827. The lysine at codon 1943 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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 RCV002355058 SCV004361770 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-15 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 1943 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 been identified in 3/251098 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.

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