Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484506 | SCV000564587 | uncertain significance | not provided | 2015-02-10 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.8144C>T at the cDNA level, p.Thr2715Ile (T2715I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACC>ATC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Thr2715Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Thr2715Ile occurs at a position that is conserved across species and is located in the EB1 binding domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Thr2715Ile is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV000122807 | SCV002270072 | uncertain significance | Familial adenomatous polyposis 1 | 2022-02-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2715 of the APC protein (p.Thr2715Ile). This variant is not present in population databases (gnomAD no frequency). 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. 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 135722). This variant has not been reported in the literature in individuals affected with APC-related conditions. |