Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075817 | SCV000106830 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability >0.99 |
| Invitae | RCV003593889 | SCV004293452 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-01-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the c.678-3 nucleotide in the MLH1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 8574961, 32356167). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Other variant(s) that result in skipping of exons 9 and 10 have been determined to be pathogenic (PMID: 32356167). This suggests that this variant may also be clinically significant and likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exons 9-10, but is expected to preserve the integrity of the reading-frame (PMID: 8574961). ClinVar contains an entry for this variant (Variation ID: 90326). This variant has been observed in individual(s) with Lynch syndrome-associated cancers (PMID: 8574961). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 8 of the MLH1 gene. It does not directly change the encoded amino acid sequence of the MLH1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. |