ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3365A>G (p.Asn1122Ser) (rs372855304)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000583866 SCV000686931 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000611424 SCV000731319 uncertain significance not specified 2016-12-21 criteria provided, single submitter clinical testing The p.Asn1122Ser variant in APC has not been previously reported in individuals with APC-associated polyposis, but has been identified in 1/8600 European chromo somes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs372855304). Computational prediction tools and conservation analysis sug gest that the p.Asn1122Ser variant may not impact the protein, though this infor mation is not predictive enough to rule out pathogenicity. In summary, the clini cal significance of the p.Asn1122Ser variant is uncertain.
Invitae RCV000646267 SCV000768035 uncertain significance Familial adenomatous polyposis 1 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1122 of the APC protein (p.Asn1122Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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. 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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