ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.1573C>T (p.Arg525Trp) (rs201804732)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573205 SCV000671102 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000554030 SCV000646493 uncertain significance Colorectal cancer 10 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 525 of the POLD1 protein (p.Arg525Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs201804732, ExAC 0.03%). This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 469206). 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 RCV000614228 SCV000712884 uncertain significance not specified 2017-02-27 criteria provided, single submitter clinical testing The p.Arg525Trp variant in POLD1 has not been previously reported in individuals with colorectal cancer, but has been identified in 3/10312 of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs201804732). Computational prediction tools and conservation analysis do no t provide strong support for or against an impact to the protein. In summary, th e clinical significance of the p.Arg525Trp variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759936 SCV000889651 uncertain significance not provided 2018-07-31 criteria provided, single submitter clinical testing

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