ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7366T>A (p.Leu2456Met)

dbSNP: rs1192175221
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777363 SCV000913225 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-01 criteria provided, single submitter clinical testing This missense variant replaces leucine with methionine at codon 2456 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250952 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003768417 SCV001519001 uncertain significance Familial adenomatous polyposis 1 2020-09-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 2456 of the APC protein (p.Leu2456Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 631200). 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: "Probably Damaging"; 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.

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