Submissions for variant NM_000038.6(APC):c.935dup (p.Glu313fs)

dbSNP: rs587781451

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129375	SCV000184140	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-05	criteria provided, single submitter	clinical testing	The c.935dupT pathogenic mutation, located in coding exon 9 of the APC gene, results from a duplication of T at nucleotide position 935, causing a translational frameshift with a predicted alternate stop codon (p.E313Gfs*14). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx	RCV000202006	SCV000293631	pathogenic	not provided	2015-12-01	criteria provided, single submitter	clinical testing	This duplication of one nucleotide in APC is denoted c.935dupT at the cDNA level and p.Glu313GlyfsX14(E313GfsX14) at the protein level. The normal sequence, with the base that is duplicated in braces, is cagG[T]GGAA with lower case letters being intronic and upper case letters being exonic. The duplication causes a frameshift, which changes a Glutamic Acid to a Glycine at codon 313 in exon 10, and creates a premature stop codon at position 14 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.
Invitae	RCV003743584	SCV000647791	pathogenic	Familial adenomatous polyposis 1	2023-03-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 141040). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu313Glyfs*14) 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).
Color Diagnostics, LLC DBA Color Health	RCV000129375	SCV001358305	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant is located in the APC protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800427	SCV002047026	likely pathogenic	not specified	2021-05-03	criteria provided, single submitter	clinical testing	This frameshift variant is predicted to cause the premature termination of APC protein synthesis. This variant has not been reported in large, multi-ethnic general populations.
Myriad Genetics, Inc.	RCV002514717	SCV004043596	pathogenic	Familial adenomatous polyposis 1	2023-04-28	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Mayo Clinic Laboratories, Mayo Clinic	RCV000202006	SCV000257038	likely pathogenic	not provided		no assertion criteria provided	research