ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.1955G>A (p.Arg652Gln) (rs778037523)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227915 SCV000287543 uncertain significance Colorectal cancer 10 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 652 of the POLD1 protein (p.Arg652Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs778037523, ExAC 0.01%). This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 239262). 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 RCV000601623 SCV000712751 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing The p.Arg652Gln variant in POLD1 has not been previously reported in individuals with colorectal cancer, but has been identified in 1/10178 of African chromosom es by the Exome Aggregation Consortium (ExAC,; db SNP rs778037523). In vitro functional studies in a rat hepatoma cell line that c arried this change at the position corresponding to human amino acid 652 provide some evidence that the p.Arg652Gln variant may impact protein function (Popanda 1999). However, these types of assays may not accurately represent biological f unction. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinica l significance of the p.Arg652Gln variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759223 SCV000888443 uncertain significance not provided 2018-06-20 criteria provided, single submitter clinical testing

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