ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7258T>C (p.Ser2420Pro)

dbSNP: rs754335788
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004570530 SCV001394877 uncertain significance Familial adenomatous polyposis 1 2024-10-22 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2420 of the APC protein (p.Ser2420Pro). This variant is present in population databases (rs754335788, gnomAD 0.003%). 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: 950940). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV002375210 SCV002671470 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-17 criteria provided, single submitter clinical testing The p.S2420P variant (also known as c.7258T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 7258. The serine at codon 2420 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004807471 SCV005429278 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-04-25 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 2420 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 1/250246 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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