ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.2797G>T (p.Val933Leu) (rs764785216)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556614 SCV000646605 uncertain significance Colorectal cancer 10 2018-08-19 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 933 of the POLD1 protein (p.Val933Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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 a POLD1-related disease. 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, this variant has uncertain impact on POLD1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000613637 SCV000731394 uncertain significance not specified 2017-02-27 criteria provided, single submitter clinical testing The p.Val933Leu variant in POLD1 has not been previously reported in individuals with colorectal cancer and was absent from large population studies. Computatio nal prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of t he p.Val933Leu variant is uncertain.

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