Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220129 | SCV000278569 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-06 | criteria provided, single submitter | clinical testing | The c.36+3A>T intronic variant results from an A to T substitution 3 nucleotides after coding exon 1 in the MUTYH gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000640392 | SCV000761983 | uncertain significance | Familial adenomatous polyposis 2 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 1 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs759654665, gnomAD 0.01%). 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: 234074). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color Diagnostics, |
RCV000220129 | SCV000908266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-30 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985859 | SCV001134476 | uncertain significance | not provided | 2023-07-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000008 (2/249422 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper MUTYH mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |
| Gene |
RCV000985859 | SCV003927531 | uncertain significance | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV000640392 | SCV004198927 | likely pathogenic | Familial adenomatous polyposis 2 | 2023-07-13 | criteria provided, single submitter | clinical testing |