ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5636G>A (p.Arg1879His) (rs145621558)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455415 SCV000540089 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant not in HGMD or ClinVar. MaxMAF is 0.11% AA not conserved in mammals - His seen in 6 non-mammals.
Invitae RCV000464959 SCV000556300 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000455415 SCV000569856 uncertain significance not specified 2016-04-04 criteria provided, single submitter clinical testing This variant is denoted POLE c.5636G>A at the cDNA level, p.Arg1879His (R1879H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLE Arg1879His was observed with an allele frequency of 0.4% (5/1322) in the African populations in 1000 Genomes. Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. POLE Arg1879His occurs at a position where amino acids with properties similar to Arginine are tolerated across species and is not located in a known functional domain (Preston 2010). 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 Arg1879His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000575608 SCV000671400 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-18 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign;Insufficient or conflicting evidence

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