ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7090G>C (p.Ala2364Pro) (rs759439613)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478252 SCV000569686 uncertain significance not provided 2016-03-21 criteria provided, single submitter clinical testing This variant is denoted ATM c.7090G>C at the cDNA level, p.Ala2364Pro (A2364P) at the protein level, and results in the change of an Alanine to a Proline (GCA>CCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ala2364Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Ala2364Pro occurs at a position that is conserved across species and is located in the FAT domain (Tavtigian 2009, Stracker 2013). Protein-based in silico analyses predict that this variant is probably damaging to protein structure and function. In addition, multiple splicing models predict that this variant may damage the nearby natural splice acceptor site. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether ATM Ala2364Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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