ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1095del (p.Asp366fs)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002457882 SCV002737783 pathogenic Hereditary cancer-predisposing syndrome 2021-11-12 criteria provided, single submitter clinical testing The c.1095delA pathogenic mutation, located in coding exon 9 of the APC gene, results from a deletion of one nucleotide at nucleotide position 1095, causing a translational frameshift with a predicted alternate stop codon (p.D366Tfs*88). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with attenuated familial adenomatous polyposis (FAP)-related disease (Ambry internal data). This alteration was identified in 2/934 French patients with FAP (Lagarde A et al. J Med Genet, 2010 Oct;47:721-2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV004565361 SCV003525838 pathogenic Familial adenomatous polyposis 1 2024-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp366Thrfs*88) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 20685668). ClinVar contains an entry for this variant (Variation ID: 1790429). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004565361 SCV004045607 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.
PreventionGenetics, part of Exact Sciences RCV003403828 SCV004103147 pathogenic APC-related disorder 2023-08-09 criteria provided, single submitter clinical testing The APC c.1095delA variant is predicted to result in a frameshift and premature protein termination (p.Asp366Thrfs*88). This variant has been reported in individuals with adenomatous polyposis coli (Supplement, Lagarde et al. 2010. PubMed ID: 20685668). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as pathogenic in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/1790429/). Frameshift variants in APC are expected to be pathogenic. This variant is interpreted as pathogenic.

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