Submissions for variant NM_006231.4(POLE):c.4117G>A (p.Ala1373Thr)

dbSNP: rs778804868

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003238317	SCV001376509	uncertain significance	not provided	2023-05-25	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. 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 POLE protein function. ClinVar contains an entry for this variant (Variation ID: 936464). This variant has not been reported in the literature in individuals affected with POLE-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1373 of the POLE protein (p.Ala1373Thr).
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238317	SCV002009576	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing