ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2023G>T (p.Ala675Ser)

dbSNP: rs753870000
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821446 SCV000962202 uncertain significance Colorectal cancer, susceptibility to, 10 2020-12-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs753870000, ExAC 0.002%). This sequence change replaces alanine with serine at codon 675 of the POLD1 protein (p.Ala675Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant has not been reported in the literature in individuals with POLD1-related disease. 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. 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.
Ambry Genetics RCV002415931 SCV002717971 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-03 criteria provided, single submitter clinical testing The p.A675S variant (also known as c.2023G>T), located in coding exon 16 of the POLD1 gene, results from a G to T substitution at nucleotide position 2023. The alanine at codon 675 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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