ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3128C>T (p.Pro1043Leu) (rs1030285956)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484691 SCV000566204 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing This variant is denoted APC c.3128C>T at the cDNA level, p.Pro1043Leu (P1043L) at the protein level, and results in the change of a Proline to a Leucine (CCT>CTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Pro1043Leu was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Pro1043Leu occurs at a position that is conserved across species and is located within 15-amino acid repeat beta-catenin binding domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Pro1043Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000646293 SCV000768061 uncertain significance Familial adenomatous polyposis 1 2017-08-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1043 of the APC protein (p.Pro1043Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 418844). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.