ClinVar Miner

Submissions for variant NM_000038.6(APC):c.937_938del (p.Glu313fs)

dbSNP: rs387906239
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000325868 SCV000329610 pathogenic not provided 2016-09-14 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in APC is denoted c.937_938delGA at the cDNA level and p.Glu313AsnfsX13 (E313NfsX13) at the protein level. The normal sequence, with the bases that are deleted in braces, is GGTG[GA]AATG. The deletion causes a frameshift, which changes a Glutamic Acid to an Asparagine at codon 313, and creates a premature stop codon at position 13 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.937_938delGA has been reported in association with both classic and attenuated FAP (Soravia 1999, Wu 2001). We consider this variant to be pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659272 SCV000781069 pathogenic Familial multiple polyposis syndrome 2016-11-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000772639 SCV000905878 pathogenic Hereditary cancer-predisposing syndrome 2020-02-24 criteria provided, single submitter clinical testing This variant deletes 2 nucleotides in exon 10 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with familial adenomatous polyposis (PMID: 9916927, 11960572). 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.
Invitae RCV003337229 SCV001210078 pathogenic Familial adenomatous polyposis 1 2022-01-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 831). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis and colorectal cancer, and a family with attenuated familial adenomatous polyposis and colorectal cancer and attenuated familial adenomatous polyposis and colorectal cancer (PMID: 9916927, 11960572, 28125075). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu313Asnfs*13) 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).
Ambry Genetics RCV000772639 SCV002682404 pathogenic Hereditary cancer-predisposing syndrome 2017-08-10 criteria provided, single submitter clinical testing The c.937_938delGA pathogenic mutation, located in coding exon 9 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 937 to 938, causing a translational frameshift with a predicted alternate stop codon (p.E313Nfs*13). This mutation has been identified in multiple individuals with FAP or AFAP (Soravia C et al. Am. J. Pathol. 1999 Jan;154:127-35; Wu G et al. Genet. Test. 2001;5:281-90). In addition to the clinical data presented in the literature, 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.
Myriad Genetics, Inc. RCV003337229 SCV004044800 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.
OMIM RCV000000874 SCV000021024 pathogenic Familial adenomatous polyposis 1 1999-01-01 no assertion criteria provided literature only
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000000874 SCV000591060 pathogenic Familial adenomatous polyposis 1 no assertion criteria provided clinical testing The APC p.Glu313AsnfsX13 variant was not identified in the literature, nor was it identified in, the 1000 Genomes Project, the NHLBI Exome Sequencing Project, the Exome Aggregation Consortium, the Genome Aggregation Database (Feb 27, 2017), Clinvitae, UMD, InSiGHT Colon Cancer Gene Variant Database (LOVD), or the Zhejiang Colon Cancer Database (LOVD). The variant was identified in dbSNP (ID: rs387906239) as “With Pathogenic allele”, GeneInsight COGR (classified as pathogenic) and ClinVar (classified as pathogenic by GeneDx and OMIM) databases. The c.937_938delGA variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 313 and leads to a premature stop codon 13 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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