ClinVar Miner

Submissions for variant NM_001127511.3(APC):c.-190G>A (rs879253785)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234994 SCV000647372 likely pathogenic Familial adenomatous polyposis 1 2017-07-24 criteria provided, single submitter clinical testing This sequence change falls in the promoter 1B region of the APC gene. It does not change the encoded amino acid sequence of the APC protein, but occurs in a region important for transcription of the APC gene. This variant is not present in population databases (1KG no frequency). This variant has been reported to segregate with colorectal polyposis, colorectal cancer and fundic gland polyps in a single family (PMID: 27087319). It has been also observed in an individual with colorectal polyposis and cancer who has a strong family history of colon cancer (Invitae). This variant is also known as c.-190G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 243008). Experimental studies have shown that this variant disrupts YY1 transcription factor binding to this promoter region in electromobility shift assays (EMSA). In addition, allelic imbalance analysis comparing sequence from cDNA and gDNA derived from patient cells shows a reduction in expression of the mutant allele (PMID: 27087319). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000234994 SCV000292339 pathogenic Familial adenomatous polyposis 1 2016-07-12 no assertion criteria provided literature only

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