Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479661 | SCV000567276 | uncertain significance | not provided | 2017-08-07 | criteria provided, single submitter | clinical testing | This variant is denoted MSH6 c.4002-10T>G or IVS9-10T>G and consists of a T>G nucleotide substitution at the -10 position of intron 9 of the MSH6 gene. Multiple in silico models predict this variant to destroy the nearby natural acceptor site, and to possibly cause abnormal gene splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 c.4002-10T>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether MSH6 c.4002-10T>G is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV001081841 | SCV000751377 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-22 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002302 | SCV004832026 | uncertain significance | Lynch syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant causes a T to G nucleotide substitution at the -10 position of intron 9 of the MSH6 gene. Splice site prediction tools suggest that this variant may impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |