ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7400C>T (p.Pro2467Leu) (rs758713824)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200356 SCV000254036 uncertain significance Familial adenomatous polyposis 1 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2467 of the APC protein (p.Pro2467Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs758713824, ExAC 0.006%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216178). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Counsyl RCV000200356 SCV000488263 uncertain significance Familial adenomatous polyposis 1 2016-02-10 criteria provided, single submitter clinical testing
Color RCV000581883 SCV000687124 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586944 SCV000694115 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The APC c.7400C>T (p.Pro2467Leu) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/121348 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714). To our knowledge, the variant has not been reported in affected individuals via publications and was not evaluated for functional impact by in vivo/vitro studies at the time of classification. One clinical diagnostic laboratory classified this variant as VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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