ClinVar Miner

Submissions for variant NM_000038.6(APC):c.583C>T (p.Gln195Ter)

dbSNP: rs749479682
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484402 SCV000568265 pathogenic not provided 2016-11-10 criteria provided, single submitter clinical testing This variant is denoted APC c.583C>T at the cDNA level and p.Gln195Ter (Q195X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in individuals with histories consistent with Familial Adenomatous Polyposis (Gavert 2002, Barkay 2005). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484402 SCV000600121 pathogenic not provided 2016-08-09 criteria provided, single submitter clinical testing
Invitae RCV003535750 SCV001236454 pathogenic Familial adenomatous polyposis 1 2019-11-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with familial adenomatous polyposis (PMID: 12007223, 16111973). ClinVar contains an entry for this variant (Variation ID: 419992). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln195*) in the APC gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002356778 SCV002650847 pathogenic Hereditary cancer-predisposing syndrome 2021-12-10 criteria provided, single submitter clinical testing The p.Q195* pathogenic mutation (also known as c.583C>T), located in coding exon 5 of the APC gene, results from a C to T substitution at nucleotide position 583. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This alteration has been reported in an Israeli polyposis cohort (Gavert N et al. Hum Mutat, 2002 Jun;19:664). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV002525822 SCV004044745 pathogenic Familial adenomatous polyposis 1 2023-04-26 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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.