ClinVar Miner

Submissions for variant NM_000038.6(APC):c.423-1G>T

dbSNP: rs397514031
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
Labcorp Genetics (formerly Invitae), Labcorp RCV004565730 SCV003525888 pathogenic Familial adenomatous polyposis 1 2022-06-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the APC gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with familial adenomatous polyposis (PMID: 10598803, 15459959). It has also been observed to segregate with disease in related individuals. Studies have shown that disruption of this splice site results in skipping of exon 5 (also known as exon 4) and introduces a premature termination codon (PMID: 15459959). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477054 SCV004219371 pathogenic not provided 2022-12-22 criteria provided, single submitter clinical testing This variant disrupts a canonical splice-acceptor site and interferes with normal APC mRNA splicing. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with familial adenomatous polyposis (FAP) (PMID: 15459959 (2004)). Functional analysis demonstrates that this variant causes exon 4 skipping (PMID: 15459959 (2004)). Based on the available information, this variant is classified as pathogenic.

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.