ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5973A>C (p.Glu1991Asp) (rs587782274)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131129 SCV000186061 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000131129 SCV000687663 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter clinical testing
GeneDx RCV000484990 SCV000567578 uncertain significance not provided 2016-03-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.5973A>C at the cDNA level, p.Glu1991Asp (E1991D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAA>GAC). This variant has not, to our knowledge, been published in the literature as either a germline pathogenic or benign variant. However, this variant has been reported as a somatic variant in clear cell renal cell carcinoma (Greenman 2007, Dalgliesh 2010). ATM Glu1991Asp 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 Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. ATM Glu1991Asp occurs at a position that is conserved across species and is located in the FAT domain (Stracker 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether ATM Glu1991Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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