ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1121G>A (p.Arg374Gln) (rs141582813)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164563 SCV000215221 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239027 SCV000297016 uncertain significance Familial multiple polyposis syndrome 2015-08-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000579391 SCV000591064 pathogenic Familial adenomatous polyposis 2014-12-23 criteria provided, single submitter clinical testing
Invitae RCV000544500 SCV000647162 uncertain significance Familial adenomatous polyposis 1 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 374 of the APC protein (p.Arg374Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs141582813, ExAC 0.003%). This variant has been reported in individuals in the Universal Mutation Database (PMID: 24599579). It has also been observed in an individual with familial adenomatous polyposis (Invitae). However, in that individual, a pathogenic allele was also identified in APC, which suggests that this c.1121G>A variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 185193). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000544500 SCV000785563 uncertain significance Familial adenomatous polyposis 1 2017-09-19 criteria provided, single submitter clinical testing

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