ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3199C>T (p.Gln1067Ter)

dbSNP: rs137854571
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004562181 SCV000959731 pathogenic Familial adenomatous polyposis 1 2023-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1067*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1777 amino acid(s) of the APC protein. 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 (FAP) (PMID: 10094547, 20685668). ClinVar contains an entry for this variant (Variation ID: 803). This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001019125 SCV001180445 pathogenic Hereditary cancer-predisposing syndrome 2019-07-29 criteria provided, single submitter clinical testing The p.Q1067* pathogenic mutation (also known as c.3199C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3199. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This alteration has been reported in several patients affected with familial adenomatous polyposis (Giarola M et al. Hum. Mutat., 1999;13:116-23; Lagarde A et al. J. Med. Genet., 2010 Oct;47:721-2; Martin-Morales L et al. PLoS ONE, 2018 Sep;13:e0203885). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV004562181 SCV004045553 pathogenic Familial adenomatous polyposis 1 2023-05-08 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.
OMIM RCV000000840 SCV000020990 pathogenic Gastric cancer 1992-06-01 no assertion criteria provided literature only

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