ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1048G>A (p.Ala350Thr) (rs371713984)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235302 SCV000293301 uncertain significance not provided 2017-07-28 criteria provided, single submitter clinical testing This variant is denoted ATM c.1048G>A at the cDNA level, p.Ala350Thr (A350T) at the protein level, and results in the change of an Alanine to a Threonine (GCA>ACA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. However, it has been reported as a somatic variant in chronic lymphocytic leukemia (CLL) tumors (Stankovic 1999, Skowronska 2012). ATM Ala350Thr 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 Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Ala350Thr occurs at a position that is conserved across species and is not located in a known functional domain (Young 2005, Tavtigian 2009, Stracker 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Ala350Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574311 SCV000665532 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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