Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003311259 | SCV004006257 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | The c.1249_1252dupAAGT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of AAGT at nucleotide positions 1249 to 1252, causing a translational frameshift with a predicted alternate stop codon (p.S418*). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
All of Us Research Program, |
RCV004009720 | SCV004840233 | pathogenic | Lynch syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This variant inserts 4 nucleotides in exon 4 of the MSH6 gene, creating a frameshift and 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. |