ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7166G>T (p.Ser2389Ile)

dbSNP: rs779287035
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003765326 SCV000260199 uncertain significance Familial adenomatous polyposis 1 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2389 of the APC protein (p.Ser2389Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 219987). 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 with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV000580609 SCV000681851 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580609 SCV001188425 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-03 criteria provided, single submitter clinical testing The p.S2389I variant (also known as c.7166G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 7166. The serine at codon 2389 is replaced by isoleucine, an amino acid with dissimilar properties. This alteration was identified in an individual diagnosed with pancreatic cancer at 55 and prostate cancer at 51 (Dudley B et al. Cancer, 2018 04;124:1691-1700). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002288827 SCV002578412 uncertain significance not provided 2022-04-06 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)

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