Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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. |