ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.504C>G (p.Phe168Leu)

gnomAD frequency: 0.00002  dbSNP: rs1060504312
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000583345 SCV000687603 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 168 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001347772 SCV001542047 uncertain significance Ataxia-telangiectasia syndrome 2024-08-07 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 168 of the ATM protein (p.Phe168Leu). This variant is not present in population databases (gnomAD 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: 490603). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV000583345 SCV002641287 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-21 criteria provided, single submitter clinical testing The p.F168L variant (also known as c.504C>G), located in coding exon 5 of the ATM gene, results from a C to G substitution at nucleotide position 504. The phenylalanine at codon 168 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well 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.
Baylor Genetics RCV004568284 SCV005056981 uncertain significance Familial cancer of breast 2024-02-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV001347772 SCV002093996 uncertain significance Ataxia-telangiectasia syndrome 2020-05-18 no assertion criteria provided clinical testing

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