ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.1696G>A (p.Glu566Lys) (rs372429157)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465945 SCV000547490 uncertain significance Colorectal cancer 10 2018-12-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 566 of the POLD1 protein (p.Glu566Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs372429157, ExAC 0.007%). This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 407947). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000608483 SCV000731310 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing The p.Glu566Lys variant in POLD1 has not been previously reported in individuals with colorectal cancer, but has been identified in 1/15260 of South Asian chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs372429157). Computational prediction tools and conservation analysis d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of the p.Glu566Lys variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759214 SCV000888433 uncertain significance not provided 2018-07-17 criteria provided, single submitter clinical testing

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