ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4063T>C (p.Ser1355Pro) (rs730881248)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159552 SCV000209520 uncertain significance not provided 2014-07-28 criteria provided, single submitter clinical testing This variant is denoted APC c.4063T>C at the cDNA level, p.Ser1355Pro (S1355P) at the protein level, and results in the change of a Serine to a Proline (TCT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser1355Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser1355Pro occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Ser1355Pro is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000774670 SCV000908550 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-19 criteria provided, single submitter clinical testing
Invitae RCV000803883 SCV000943770 uncertain significance Familial adenomatous polyposis 1 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1355 of the APC protein (p.Ser1355Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181804). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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