ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.197C>G (p.Ala66Gly)

gnomAD frequency: 0.00001  dbSNP: rs199792522
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460501 SCV000547601 uncertain significance Colorectal cancer, susceptibility to, 10 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 66 of the POLD1 protein (p.Ala66Gly). This variant is present in population databases (rs199792522, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 408049). 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 not expected to disrupt POLD1 protein function with a negative 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.
GeneDx RCV000485401 SCV000569834 uncertain significance not provided 2024-09-23 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in a patient with breast cancer (PMID: 35264596); This variant is associated with the following publications: (PMID: 35264596)
Mendelics RCV003492057 SCV001141126 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003168791 SCV003909022 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-06 criteria provided, single submitter clinical testing The p.A66G variant (also known as c.197C>G), located in coding exon 1 of the POLD1 gene, results from a C to G substitution at nucleotide position 197. The alanine at codon 66 is replaced by glycine, 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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