Submissions for variant NM_000038.6(APC):c.1526del (p.Thr509fs)

dbSNP: rs1064794092

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485159	SCV000567796	pathogenic	not provided	2015-09-02	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in APC is denoted c.1526delC at the cDNA level and p.Thr509IlefsX5 (T509IfsX5) at the protein level. The normal sequence, with the base that is deleted in braces, is TTGA[C]TTTTG. The deletion causes a frameshift, which changes a Threonine to an Isoleucine at codon 509, and creates a premature stop codon at position 5 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004564172	SCV000818914	pathogenic	Familial adenomatous polyposis 1	2018-08-09	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 419764). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr509Ilefs*5) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV004564172	SCV004045645	pathogenic	Familial adenomatous polyposis 1	2023-05-01	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.