Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003337278 | SCV000552674 | pathogenic | Familial adenomatous polyposis 1 | 2023-08-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 411488). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 17411426, 20223039, 20685668). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser457*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). |
Gene |
RCV000481642 | SCV000568270 | pathogenic | not provided | 2017-12-07 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted APC c.1370C>G at the cDNA level and p.Ser457Ter (S457X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Ser457Ter has been observed in multiple individuals with Familial Adenomatous Polyposis (FAP) or Attenuated FAP, including at least two related individuals with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (Wallis 1994, Michils 2002, Friedl 2005, Stekrova 2007). Based on currently available evidence, we consider this variant to be pathogenic. |
Ambry Genetics | RCV000491762 | SCV000579843 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | The p.S457* pathogenic mutation (also known as c.1370C>G), located in coding exon 10 of the APC gene, results from a C to G substitution at nucleotide position 1370. This changes the amino acid from a serine to a stop codon within coding exon 10. This mutation has been identified in multiple individuals/families with familial adenomatous polyposis or attenuated familial adenomatous polyposis (Friedl W et al. Hered Cancer Clin Pract. 2005 Sep;3:95-114; Stekrova J et al. BMC Med. Genet. 2007;8:16; Lagarde A et al. J. Med. Genet. 2010 Oct;47:721-2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
ARUP Laboratories, |
RCV000508095 | SCV000602501 | pathogenic | not specified | 2016-09-05 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000481642 | SCV002563847 | pathogenic | not provided | 2020-07-01 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003337278 | SCV004044729 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-01 | 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. |