ClinVar Miner

Submissions for variant NM_000038.6(APC):c.643C>T (p.Gln215Ter)

dbSNP: rs137854577
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000202265 SCV000292709 pathogenic not provided 2016-11-14 criteria provided, single submitter clinical testing This variant is denoted APC c.643C>T at the cDNA level and p.Gln215Ter (Q215X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), 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 association with polyposis and brain cancer (Miyoshi 1992, Hamilton 1995) and is considered pathogenic.
Ambry Genetics RCV000491571 SCV000579931 pathogenic Hereditary cancer-predisposing syndrome 2016-11-15 criteria provided, single submitter clinical testing The p.Q215* pathogenic mutation (also known as c.643C>T), located in coding exon 5 of the APC gene, results from a C to T substitution at nucleotide position 643. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This alteration was identified in 1/79 unrelated patients with a clinical diagnosis of Familial Adenomatous Polyposis (FAP) (Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992 May;89:4452-6). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507194 SCV000602514 pathogenic not specified 2016-09-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000202265 SCV000805453 pathogenic not provided 2015-07-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000000853 SCV000946143 pathogenic Familial adenomatous polyposis 1 2024-01-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln215*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis, colorectal cancer or brain cancer (PMID: 1316610, 7661930, 28944238). This variant is also known as c.673C>T, p.Gln225*. ClinVar contains an entry for this variant (Variation ID: 814). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002490286 SCV002801185 pathogenic Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2021-08-19 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002490286 SCV003920193 pathogenic Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2021-03-30 criteria provided, single submitter clinical testing APC NM_000038.5 exon 6 p.Gln215* (c.643C>T): This variant (also referred to as Gln225*) has been reported in the literature in multiple individuals with familial adenomatous polyposis (FAP), as well as in an individual who also had brain cancer (Miyoshi 1992 PMID:1316610, Hamilton 1995 PMID:7661930, DeRycke 2017 PMID:28944238). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:814). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or loss of allelic expression through nonsense-mediated mRNA decay. Loss of function variants are a known mechanism of disease for this gene (Zhang 2017 PMID:28423402). In summary, this variant is classified as pathogenic based on the data above.
Myriad Genetics, Inc. RCV000000853 SCV004045597 pathogenic Familial adenomatous polyposis 1 2023-04-27 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.
Baylor Genetics RCV000000853 SCV004200496 pathogenic Familial adenomatous polyposis 1 2021-05-05 criteria provided, single submitter clinical testing
OMIM RCV000000853 SCV000021003 pathogenic Familial adenomatous polyposis 1 1995-03-30 no assertion criteria provided literature only
OMIM RCV000000854 SCV000021004 pathogenic Brain tumor-polyposis syndrome 2 1995-03-30 no assertion criteria provided literature only
Mayo Clinic Laboratories, Mayo Clinic RCV000202265 SCV000257023 pathogenic not provided no assertion criteria provided research

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