Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410065 | SCV000487375 | likely pathogenic | Familial adenomatous polyposis 2 | 2016-08-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000410065 | SCV001390430 | likely pathogenic | Familial adenomatous polyposis 2 | 2024-02-12 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 14 of the MUTYH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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: 371681). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV002392934 | SCV002697063 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-18 | criteria provided, single submitter | clinical testing | The c.1477-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 15 of the MUTYH gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is unavailable. The exact functional effect of the missing amino acids at the 3' terminus of the MUTYH gene, which impacts the last 14 AA of the protein, is unknown; however, the impacted region is critical for protein function (Ambry internal data; Wang L et al. J. Biol. Chem., 2015 Jul;290:17096-105). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Baylor Genetics | RCV000410065 | SCV005056040 | likely pathogenic | Familial adenomatous polyposis 2 | 2024-03-07 | criteria provided, single submitter | clinical testing |