ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4151A>G (p.His1384Arg)

gnomAD frequency: 0.00001  dbSNP: rs757172522
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221533 SCV000275226 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-10 criteria provided, single submitter clinical testing The p.H1384R variant (also known as c.4151A>G), located in coding exon 27 of the ATM gene, results from an A to G substitution at nucleotide position 4151. The histidine at codon 1384 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is 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.
Mendelics RCV000709181 SCV000838537 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000709181 SCV000935953 uncertain significance Ataxia-telangiectasia syndrome 2024-12-10 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1384 of the ATM protein (p.His1384Arg). 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: 231391). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. 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 RCV000221533 SCV001354797 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-15 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 1384 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. 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 been identified in 1/251298 chromosomes 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. RCV000709181 SCV002079203 uncertain significance Ataxia-telangiectasia syndrome 2021-10-11 no assertion criteria provided clinical testing

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