Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000216618 | SCV000278479 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.K155* pathogenic mutation (also known as c.463A>T), located in coding exon 6 of the MUTYH gene, results from an A to T substitution at nucleotide position 463. This changes the amino acid from a lysine to a stop codon within coding exon 6. However, this change occurs in the first base pair of coding exon 6, which means it may have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This alteration is expected to result in an abnormal protein or in a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV000485126 | SCV000570773 | pathogenic | not provided | 2024-09-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000707329 | SCV000836421 | pathogenic | Familial adenomatous polyposis 2 | 2023-09-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 234000). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Lys155*) 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). |
| Baylor Genetics | RCV000707329 | SCV004199434 | likely pathogenic | Familial adenomatous polyposis 2 | 2022-01-17 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000216618 | SCV004358591 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 6 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 reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250418 chromosomes 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. |