Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985861 | SCV001134479 | pathogenic | not provided | 2019-04-01 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. Occurs in multiple cases with a recessive pathogenic variant in the same gene. |
| Labcorp Genetics |
RCV001218539 | SCV001390425 | pathogenic | Familial adenomatous polyposis 2 | 2021-07-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individuals affected with clinical features of MUTYH-associated polyposis. In these individuals, a second pathogenic variant in the MUTYH gene was also reported (PMID: 16890597, 18091433). This variant is also known as W160X in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp174*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002346192 | SCV002646729 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-11-11 | criteria provided, single submitter | clinical testing | The p.W174* pathogenic mutation (also known as c.521G>A), located in coding exon 7 of the MUTYH gene, results from a G to A substitution at nucleotide position 521. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. This mutation (designated as W160X) has been reported in conjunction with a second truncating MUTYH mutation in a male diagnosed with 100 adenomatous polyps at age 35 (Di Gregorio C et al, Gastroenterology 2006 Aug; 131(2):439-44). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |