Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478455 | SCV000571561 | likely pathogenic | not provided | 2016-08-31 | criteria provided, single submitter | clinical testing | This variant is denoted MUTYH c.35G>A at the cDNA level and p.Trp12Ter (W12X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic. |
| Invitae | RCV001209233 | SCV001380657 | pathogenic | Familial adenomatous polyposis 2 | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp12*) 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: 422159). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV003168963 | SCV003867800 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.W12* variant (also known as c.35G>A), located in coding exon 1 of the MUTYH gene, results from a G to A substitution at nucleotide position 35. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. The predicted stop codon occurs in the 5’ end of theMUTYH gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Baylor Genetics | RCV001209233 | SCV004198837 | likely pathogenic | Familial adenomatous polyposis 2 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000478455 | SCV004222083 | likely pathogenic | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | NMD is expected as a result of this variant, and therefore the loss of a functional protein. This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |