Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000640364 | SCV000761953 | pathogenic | Familial adenomatous polyposis 2 | 2023-08-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 533306). This sequence change creates a premature translational stop signal (p.Trp427Serfs*22) 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 premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 27978560). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV003352961 | SCV004055766 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-02 | criteria provided, single submitter | clinical testing | The c.1280_1289del10 pathogenic mutation, located in coding exon 13 of the MUTYH gene, results from a deletion of 10 nucleotides at nucleotide positions 1280 to 1289, causing a translational frameshift with a predicted alternate stop codon (p.W427Sfs*22). This alteration has been previously identified in an individual from a North American cohort of individuals with early onset colon cancer (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |
Baylor Genetics | RCV000640364 | SCV004199437 | likely pathogenic | Familial adenomatous polyposis 2 | 2021-10-19 | criteria provided, single submitter | clinical testing |