ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4331T>A (p.Leu1444Gln)

dbSNP: rs2082676298
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001234624 SCV001407279 uncertain significance Ataxia-telangiectasia syndrome 2019-09-09 criteria provided, single submitter clinical testing This sequence change replaces leucine with glutamine at codon 1444 of the ATM protein (p.Leu1444Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV003284094 SCV004007230 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-27 criteria provided, single submitter clinical testing The p.L1444Q variant (also known as c.4331T>A), located in coding exon 28 of the ATM gene, results from a T to A substitution at nucleotide position 4331. The leucine at codon 1444 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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