ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4618G>T (p.Asp1540Tyr)

gnomAD frequency: 0.00001  dbSNP: rs778622948
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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 RCV000627940 SCV000748825 uncertain significance Ataxia-telangiectasia syndrome 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 1540 of the ATM protein (p.Asp1540Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs778622948, ExAC 0.008%). 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: "Deleterious"; 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 RCV002334040 SCV002639084 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-12 criteria provided, single submitter clinical testing The p.D1540Y variant (also known as c.4618G>T), located in coding exon 30 of the ATM gene, results from a G to T substitution at nucleotide position 4618. The aspartic acid at codon 1540 is replaced by tyrosine, an amino acid with highly dissimilar 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.
Natera, Inc. RCV000627940 SCV002082949 uncertain significance Ataxia-telangiectasia syndrome 2019-10-28 no assertion criteria provided clinical testing

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