ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.632G>A (p.Arg211His) (rs373192520)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558072 SCV000646688 uncertain significance Colorectal cancer 10 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 211 of the POLD1 protein (p.Arg211His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs373192520, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 439259). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000507707 SCV000731334 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing The p.Arg211His variant in POLD1 has not been previously reported in individuals with colorectal cancer, but has been identified in 8/63688 of European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs373192520). Computational prediction tools and conservation analysis sugg est that the p.Arg211His variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical s ignificance of the p.Arg211His variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507707 SCV000601949 uncertain significance not specified 2016-12-31 criteria provided, single submitter clinical testing

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