ClinVar Miner

Submissions for variant NM_000038.6(APC):c.304T>C (p.Ser102Pro)

dbSNP: rs753302494
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561562 SCV000667771 likely benign Hereditary cancer-predisposing syndrome 2023-02-27 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.
Color Diagnostics, LLC DBA Color Health RCV000561562 SCV001353783 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-16 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 102 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 hereditary cancer in the literature. This variant has been identified in 2/251466 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.
Invitae RCV003744560 SCV001387335 uncertain significance Familial adenomatous polyposis 1 2024-01-31 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 102 of the APC protein (p.Ser102Pro). This variant is present in population databases (rs753302494, gnomAD 0.006%). 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: 482497). 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.
Sema4, Sema4 RCV000561562 SCV002531771 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-30 criteria provided, single submitter curation
Baylor Genetics RCV002530295 SCV004201602 uncertain significance Familial adenomatous polyposis 1 2023-07-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478245 SCV004222406 uncertain significance not provided 2023-06-09 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000008 (2/251466 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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