ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4060delinsAA (p.Phe1354fs)

dbSNP: rs1554085479
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000503626 SCV000591164 pathogenic Carcinoma of colon no assertion criteria provided clinical testing The APC, p.Phe1354AsnfsX21 variant was not identified in the literature nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, HGMD, COSMIC, MutDB, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, the ClinVar database, GeneInsight VariantWire database and UMD databases. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. The p.Phe1354AsnfsX21 deletion/insertion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1354 and leads to a premature stop codon 21 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in familial adenomatous polyposis and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

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