Submissions for variant NM_002691.4(POLD1):c.2824C>T (p.Pro942Ser)

dbSNP: rs1203736050

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000560470	SCV000646608	uncertain significance	Colorectal cancer, susceptibility to, 10	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 942 of the POLD1 protein (p.Pro942Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 469304). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POLD1 protein function with a positive predictive value of 80%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759229	SCV000888452	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000759229	SCV001785801	uncertain significance	not provided	2020-06-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25583476)
Ambry Genetics	RCV002438439	SCV002752231	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-16	criteria provided, single submitter	clinical testing	The p.P942S variant (also known as c.2824C>T), located in coding exon 22 of the POLD1 gene, results from a C to T substitution at nucleotide position 2824. The proline at codon 942 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.