Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011635 | SCV001171980 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-21 | criteria provided, single submitter | clinical testing | The p.T483I variant (also known as c.1448C>T), located in coding exon 14 of the POLE gene, results from a C to T substitution at nucleotide position 1448. The threonine at codon 483 is replaced by isoleucine, 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. |
Invitae | RCV003657493 | SCV002255412 | uncertain significance | not provided | 2022-07-25 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 483 of the POLE protein (p.Thr483Ile). 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: 819244). 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. |