ClinVar Miner

Submissions for variant NM_000038.6(APC):c.645G>C (p.Gln215His) (rs1060503295)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470315 SCV000552571 uncertain significance Familial adenomatous polyposis 1 2017-07-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 215 of the APC protein (p.Gln215His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. It also falls at the last nucleotide of exon 6 of the APC coding sequence. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 411420). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098) but according to multiple splice site algorithms this particular variant is not predicted to significantly affect splicing. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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