Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000576676 | SCV000678201 | likely pathogenic | Familial adenomatous polyposis 2 | 2017-01-24 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000777015 | SCV000912693 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV000777015 | SCV001182029 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-14 | criteria provided, single submitter | clinical testing | The p.E118* pathogenic mutation (also known as c.352G>T), located in coding exon 4 of the MUTYH gene, results from a G to T substitution at nucleotide position 352. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV000576676 | SCV001225046 | pathogenic | Familial adenomatous polyposis 2 | 2023-03-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 487453). 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 creates a premature translational stop signal (p.Glu118*) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000576676 | SCV002548142 | likely pathogenic | Familial adenomatous polyposis 2 | 2022-05-23 | criteria provided, single submitter | clinical testing | Variant summary: MUTYH c.352G>T (p.Glu118X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251374 control chromosomes. To our knowledge, no occurrence of c.352G>T in individuals affected with MUTYH-Associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |