ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4057A>G (p.Ser1353Gly) (rs141619382)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000988935 SCV000289364 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000256048 SCV000322188 uncertain significance not specified 2017-09-13 criteria provided, single submitter clinical testing This variant is denoted POLE c.4057A>G at the cDNA level, p.Ser1353Gly (S1353G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or benign polymorphism. However, it has been reported as a somatic variant in Burkitt's lymphoma (Schmitz 2012). POLE Ser1353Gly was observed with an allele frequency of 0.2% (13/8600) in European Americans in the NHLBI Exome Sequencing Project. Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. POLE Ser1353Gly occurs at a position where amino acids with properties similar to Serine are tolerated across species and is not located in a known functional domain. 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 POLE Ser1353Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000256048 SCV000602040 likely benign not specified 2017-03-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571135 SCV000671222 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
PreventionGenetics,PreventionGenetics RCV000679629 SCV000806771 uncertain significance not provided 2017-01-10 criteria provided, single submitter clinical testing
Mendelics RCV000988935 SCV001138871 uncertain significance Colorectal cancer, susceptibility to, 12 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679629 SCV001148887 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000571135 SCV000805300 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-05 no assertion criteria provided clinical testing

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