ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1021G>C (p.Ala341Pro)

dbSNP: rs137860861
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003654299 SCV000543977 uncertain significance not provided 2024-06-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 341 of the POLE protein (p.Ala341Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 405664). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Ambry Genetics RCV000564047 SCV000674354 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-16 criteria provided, single submitter clinical testing The p.A341P variant (also known as c.1021G>C) is located in coding exon 11 of the POLE gene. The alanine at codon 341 is replaced by proline, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 11. This amino acid position is poorly conserved in available vertebrate species. 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.
Baylor Genetics RCV000460044 SCV004203529 uncertain significance Colorectal cancer, susceptibility to, 12 2023-09-29 criteria provided, single submitter clinical testing

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