ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1440A>T (p.Gln480His) (rs863224537)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198684 SCV000253989 uncertain significance Familial adenomatous polyposis 1 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 480 of the APC protein (p.Gln480His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. 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: 216150). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000780851 SCV000918462 uncertain significance not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The APC c.1440A>T (p.Gln480His) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 3/4 in silico tools (SNPsandGO not captured due to low reliability index). This variant is absent in 245924 control chromosomes (gnomAD). One clinical laboratory in ClinVar and a reputable database (UMD) have classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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