ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5894A>C (p.His1965Pro) (rs773776516)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000332846 SCV000452032 uncertain significance APC-Associated Polyposis Disorders 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000474627 SCV000552557 uncertain significance Familial adenomatous polyposis 1 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 1965 of the APC protein (p.His1965Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is present in population databases (rs773776516, ExAC 0.01%) but has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 350416). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567246 SCV000667225 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-02 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000567246 SCV001360142 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-20 criteria provided, single submitter clinical testing

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