Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000196963 | SCV000253854 | pathogenic | Familial adenomatous polyposis 2 | 2024-09-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro405Leufs*123) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 216080). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000486695 | SCV000571449 | likely pathogenic | not provided | 2025-03-24 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in abnormal protein length as the last 145 amino acids are replaced with 122 different amino acids, and other similar variants have been reported in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV001010324 | SCV001170501 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-22 | criteria provided, single submitter | clinical testing | The c.1214_1224del11 pathogenic mutation, located in coding exon 13 of the MUTYH gene, results from a deletion of 11 nucleotides at nucleotide positions 1214 to 1224, causing a translational frameshift with a predicted alternate stop codon (p.P405Lfs*123). This alteration occurs at the 3' terminus of the MUTYH gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 145 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV000196963 | SCV004198905 | likely pathogenic | Familial adenomatous polyposis 2 | 2023-08-06 | criteria provided, single submitter | clinical testing |