ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.7C>G (p.Leu3Val)

dbSNP: rs1018143132
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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 RCV003655117 SCV000653478 uncertain significance not provided 2023-05-20 criteria provided, single submitter clinical testing 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 473831). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the POLE protein (p.Leu3Val).
Counsyl RCV000550377 SCV000786409 uncertain significance Colorectal cancer, susceptibility to, 12 2018-04-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV004024252 SCV003737679 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-15 criteria provided, single submitter clinical testing The c.7C>G (p.L3V) alteration is located in exon 1 (coding exon 1) of the POLE gene. This alteration results from a C to G substitution at nucleotide position 7, causing the leucine (L) at amino acid position 3 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004543223 SCV004777787 uncertain significance POLE-related disorder 2024-01-16 no assertion criteria provided clinical testing The POLE c.7C>G variant is predicted to result in the amino acid substitution p.Leu3Val. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. In the ClinVar database, this variant is reported as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/473831/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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