Submissions for variant NM_000038.6(APC):c.4508del (p.Ser1503fs)

dbSNP: rs1580649018

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001022604	SCV001184359	pathogenic	Hereditary cancer-predisposing syndrome	2019-08-07	criteria provided, single submitter	clinical testing	The c.4508delC pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 4508, causing a translational frameshift with a predicted alternate stop codon (p.S1503Yfs*4). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001260339	SCV001437271	likely pathogenic	Familial multiple polyposis syndrome	2020-09-03	criteria provided, single submitter	clinical testing	Variant summary: APC c.4508delC (p.Ser1503TyrfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein. The variant was absent in 250312 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4508delC in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.