ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6278C>T (p.Ser2093Phe) (rs879254172)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236754 SCV000293707 uncertain significance not provided 2015-12-16 criteria provided, single submitter clinical testing This variant is denoted APC c.6278C>T at the cDNA level, p.Ser2093Phe (S2093F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser2093Phe was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser2093Phe occurs at a position that is conserved across species and is not located in a known functional domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Ser2093Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000525924 SCV000647633 uncertain significance Familial adenomatous polyposis 1 2017-08-11 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2093 of the APC protein (p.Ser2093Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. 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: 246238). 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 disruptive, 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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