ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5419A>G (p.Lys1807Glu)

dbSNP: rs1591712583
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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 RCV001362558 SCV001558584 uncertain significance Ataxia-telangiectasia syndrome 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1807 of the ATM protein (p.Lys1807Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ataxia-telangiectasia (A-T) (PMID: 19431188). ClinVar contains an entry for this variant (Variation ID: 1054109). 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. Experimental studies have shown that this missense change affects ATM function (PMID: 19431188). 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.
Fulgent Genetics, Fulgent Genetics RCV002499733 SCV002783285 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2021-09-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV004681142 SCV005180352 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-14 criteria provided, single submitter clinical testing The p.K1807E variant (also known as c.5419A>G), located in coding exon 35 of the ATM gene, results from an A to G substitution at nucleotide position 5419. The lysine at codon 1807 is replaced by glutamic acid, an amino acid with similar properties. This alteration was seen in 1/732 breast cancer patients in a Turkish population (Akcay IM et al. Int J Cancer, 2021 Jan;148:285-295). In a functional study, this alteration showed partial loss of kinase activity (Barone G et al. Hum Mutat, 2009 Aug;30:1222-30). 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 variant remains unclear.

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