ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2411A>G (p.Asn804Ser) (rs775727621)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476763 SCV000552543 uncertain significance Familial adenomatous polyposis 1 2018-05-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 804 of the APC protein (p.Asn804Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs775727621, ExAC 0.001%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 411401). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV000483927 SCV000570910 uncertain significance not provided 2018-11-28 criteria provided, single submitter clinical testing This variant is denoted APC c.2411A>G at the cDNA level, p.Asn804Ser (N804S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has been observed in at least one individual with breast cancer (Tung 2015). APC Asn804Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Asn804Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000775137 SCV000909253 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-20 criteria provided, single submitter clinical testing

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