ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7193C>T (p.Ser2398Phe) (rs150882838)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168076 SCV000218730 uncertain significance Familial adenomatous polyposis 1 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2398 of the APC protein (p.Ser2398Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs150882838, ExAC 0.03%). This variant has been reported in the literature in an individual affected with colon cancer (PMID: 25559809). ClinVar contains an entry for this variant (Variation ID: 188173). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Counsyl RCV000168076 SCV000488341 uncertain significance Familial adenomatous polyposis 1 2016-03-02 criteria provided, single submitter clinical testing
GeneDx RCV000657134 SCV000570264 uncertain significance not provided 2018-04-03 criteria provided, single submitter clinical testing This variant is denoted APC c.7193C>T at the cDNA level, p.Ser2398Phe (S2398F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has been observed in at least one individual with colorectal cancer and another with breast and/or ovarian cancer (Chubb 2015, Maxwell 2016). APC Ser2398Phe was observed at an allele frequency of 0.05% (12/23,990) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the Basic domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Ser2398Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000491288 SCV000579799 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000491288 SCV000681853 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing
Mendelics RCV000168076 SCV000838146 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657134 SCV000887550 uncertain significance not provided 2018-04-03 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000486411 SCV000691762 uncertain significance not specified no assertion criteria provided clinical testing

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