ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6374A>G (p.His2125Arg) (rs730881381)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159746 SCV000209761 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing This variant is denoted ATM c.6374A>G at the cDNA level, p.His2125Arg (H2125R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). This variant was observed at the somatic level in prostate cancer and mantle cell lymphoma tumor tissue samples (Kridel 2012, Grasso 2012, Meissner 2013). Fang et al. (2003) reported that ATM His2125Arg was likely present in the germline of a mantle cell lymphoma patient based on the presence of wild-type alleles in the tumor. ATM His2125Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Histidine and Arginine share similar properties, this is considered a conservative amino acid substitution. ATM His2125Arg occurs at a position that is conserved across species and is located in the FAT domain (Tavtigian 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM His2125Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.

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