ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.2954G>C (p.Arg985Pro) (rs749159160)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460737 SCV000547661 uncertain significance Colorectal cancer 10 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 985 of the POLD1 protein (p.Arg985Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 408108). 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 RCV000506861 SCV000731486 uncertain significance not specified 2017-07-18 criteria provided, single submitter clinical testing The p.Arg985Pro variant in POLD1 has not been previously reported in the literat ure in individuals with colorectal cancer but has been reported in ClinVar (Vari ation ID 408108). This variant was absent from large population studies. Computa tional prediction tools and conservation analysis suggest that the p.Arg985Pro v ariant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg98 5Pro variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506861 SCV000601928 uncertain significance not specified 2016-11-17 criteria provided, single submitter clinical testing

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