Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491089 | SCV000580116 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-01-10 | criteria provided, single submitter | clinical testing | The c.3356_3358delAAGinsGAT variant, located in coding exon 5 of the MSH6 gene, results from an in-frame deletion of AAG and insertion of GAT between nucleotide positions 3356 and 3358. This changes the glutamate at codon 1120 to a stop codon within coding exon 5. This nucleotide region is well conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Myriad Genetics, |
RCV003449288 | SCV004185879 | pathogenic | Lynch syndrome 5 | 2023-08-22 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| All of Us Research Program, |
RCV004003452 | SCV004839343 | pathogenic | Lynch syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | This variant deletes 3 nucleotides AAG and inserts 3 new nucleotides GAT in exon 5 of the MSH6 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, 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). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |