ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1232T>C (p.Val411Ala)

dbSNP: rs1031999052
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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 RCV003654292 SCV000543954 uncertain significance not provided 2023-09-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 411 of the POLE protein (p.Val411Ala). 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: 405643). 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 POLE protein function. 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 RCV002365609 SCV002662923 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-19 criteria provided, single submitter clinical testing The p.V411A variant (also known as c.1232T>C), located in coding exon 13 of the POLE gene, results from a T to C substitution at nucleotide position 1232. The valine at codon 411 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004567961 SCV005056556 uncertain significance Colorectal cancer, susceptibility to, 12 2023-12-02 criteria provided, single submitter clinical testing

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