ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5333C>G (p.Pro1778Arg)

dbSNP: rs952662066
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777483 SCV000913345 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-06 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 1778 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV001788346 SCV002030129 uncertain significance Familial adenomatous polyposis 1 2021-07-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001788346 SCV002288971 uncertain significance Familial adenomatous polyposis 1 2021-09-01 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 631302). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 1778 of the APC protein (p.Pro1778Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.
Ambry Genetics RCV000777483 SCV005033220 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-22 criteria provided, single submitter clinical testing The p.P1778R variant (also known as c.5333C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5333. The proline at codon 1778 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.