ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3379C>T (p.Gln1127Ter)

dbSNP: rs1765409926
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003336302 SCV001227274 pathogenic Familial adenomatous polyposis 1 2019-12-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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." 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. This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Gln1127*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1717 amino acids of the APC protein.
Ambry Genetics RCV002451265 SCV002614429 pathogenic Hereditary cancer-predisposing syndrome 2017-11-21 criteria provided, single submitter clinical testing The p.Q1127* pathogenic mutation (also known as c.3379C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3379. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This mutation was identified in multiple probands with a clinical diagnosis of FAP or AFAP (Friedl W and Aretz S Hered Cancer Clin Pract, 2005 Sep;3:95-114; Jarry J et al. Fam. Cancer, 2011 Dec;10:659-65). 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. RCV003336302 SCV004045087 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.

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