ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4100A>G (p.Gln1367Arg)

gnomAD frequency: 0.00001  dbSNP: rs1399790840
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532247 SCV000647496 uncertain significance Familial adenomatous polyposis 1 2023-08-02 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 469951). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1367 of the APC protein (p.Gln1367Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573595 SCV000667461 likely benign Hereditary cancer-predisposing syndrome 2023-02-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000611032 SCV000731322 uncertain significance not specified 2016-12-21 criteria provided, single submitter clinical testing The p.Gln1367Arg variant in APC has not been previously reported in individuals with APC-associated polyposis, but has been identified in 2/126198 of European c hromosomes by the genome Aggregation Database (gnomAD, http:// http://gnomad.bro adinstitute.org). Although the affected amino acid is well conserved in evolutio n, computational pathogenicity prediction tools suggest that this change may not affect the protein. In summary, the clinical significance of the p.Gln1367Arg v ariant is uncertain.
Counsyl RCV000532247 SCV000786322 uncertain significance Familial adenomatous polyposis 1 2018-04-06 criteria provided, single submitter clinical testing
GeneDx RCV002508225 SCV002817832 uncertain significance not provided 2022-06-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)
Myriad Genetics, Inc. RCV002231976 SCV004018086 uncertain significance Familial adenomatous polyposis 1 2023-02-14 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
PreventionGenetics, part of Exact Sciences RCV003403314 SCV004102920 uncertain significance APC-related condition 2023-09-27 criteria provided, single submitter clinical testing The APC c.4100A>G variant is predicted to result in the amino acid substitution p.Gln1367Arg. This variant has been reported in an individual with proximal colon cancer (Patient ID 118201, Chubb et al. 2015. PubMed ID: 25559809). This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-112175391-A-G) and is reported as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/469951/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV000532247 SCV004197564 uncertain significance Familial adenomatous polyposis 1 2023-10-27 criteria provided, single submitter clinical testing

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