Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020427 | SCV001181906 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-27 | criteria provided, single submitter | clinical testing | The c.348G>T variant (also known as p.R116R), located in coding exon 3 of the MUTYH gene, results from a G to T substitution at nucleotide position 348. This nucleotide substitution does not change the at codon 116. However, this change occurs in the last base pair of coding exon 3, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003614073 | SCV004424773 | uncertain significance | Familial adenomatous polyposis 2 | 2023-06-05 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 3 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 823834). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 116 of the MUTYH mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MUTYH protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |