Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001050038 | SCV001214125 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of two cryptic splice sites and introduces a premature termination codon (PMID: 29568967). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 846676). Disruption of this splice site has been observed in individuals with clinical features of Lynch syndrome (PMID: 9311737, 26517685, 29568967). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 1 of the MSH2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |