Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000234994 | SCV000647372 | pathogenic | Familial adenomatous polyposis 1 | 2024-01-09 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the APC gene. It does not change the encoded amino acid sequence of the APC protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of familial adenomatous polyposis (PMID: 27087319; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.-190G>A. ClinVar contains an entry for this variant (Variation ID: 243008). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects APC function (PMID: 27087319). For these reasons, this variant has been classified as Pathogenic. |
| Centogene AG - |
RCV000234994 | SCV001426488 | pathogenic | Familial adenomatous polyposis 1 | criteria provided, single submitter | clinical testing | ||
| Center for Genomic Medicine, |
RCV004020914 | SCV005016551 | likely pathogenic | Periampullary adenoma | 2024-03-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004020915 | SCV005038199 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-29 | criteria provided, single submitter | clinical testing | The c.-190G>A variant is located in the 5' untranslated region (5’ UTR) of the APC gene. This variant results from a G to A substitution 190 bases upstream from the first translated codon. This alteration has been detected in multiple individuals with a personal and/or family history of colon polyposis and/or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and was shown to segregate with disease in at least one family (Li J et al. Am J Hum Genet, 2016 May;98:830-842; Bertoli-Avella AM et al. Eur J Hum Genet, 2021 Jan;29:141-153). The alteration impacts a highly-conserved nucleotide within the YY1 binding motif of APC promoter 1B, and authors demonstrated disrupted protein binding associated with c.-190G>A (Li J et al. Am J Hum Genet, 2016 May;98:830-842). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| OMIM | RCV000234994 | SCV000292339 | pathogenic | Familial adenomatous polyposis 1 | 2016-07-12 | no assertion criteria provided | literature only |