ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3702T>G (p.Phe1234Leu)

dbSNP: rs876659605
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215477 SCV000276246 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-20 criteria provided, single submitter clinical testing The p.F1234L variant (also known as c.3702T>G), located in coding exon 24 of the ATM gene, results from a T to G substitution at nucleotide position 3702. The phenylalanine at codon 1234 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000531518 SCV000622443 uncertain significance Ataxia-telangiectasia syndrome 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 1234 of the ATM protein (p.Phe1234Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. 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. ClinVar contains an entry for this variant (Variation ID: 232184). 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: "Probably 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.
Color Diagnostics, LLC DBA Color Health RCV000215477 SCV001356367 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 1234 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 ATM-related disorders in the literature. This variant has not been identified 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.
Natera, Inc. RCV000531518 SCV002078959 uncertain significance Ataxia-telangiectasia syndrome 2020-09-23 no assertion criteria provided clinical testing

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