Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001032860 | SCV001196167 | pathogenic | Familial adenomatous polyposis 2 | 2019-12-04 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 4-16 of the MUTYH gene. The 5' boundary is likely confined to intron 3. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Similar deletions of exons 4-16 have been reported in the homozygous and compound heterozygous state in individuals affected with polyposis and colorectal cancer (PMID: 21962078, 23561487, 24953332). This variant disrupts the p.Tyr179 amino acid residue in MUTYH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12606733, 16557584, 17489848, 11818965, 18534194, 19953527). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |