Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001180441 | SCV001345374 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 14 of the MSH2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV001180441 | SCV002732971 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-06 | criteria provided, single submitter | clinical testing | The c.2332delT pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2332, causing a translational frameshift with a predicted alternate stop codon (p.C778Afs*34). 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. |
| Myriad Genetics, |
RCV003449590 | SCV004187962 | pathogenic | Lynch syndrome 1 | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Laboratory for Molecular Medicine, |
RCV004017792 | SCV004847755 | likely pathogenic | Lynch syndrome | 2019-05-08 | criteria provided, single submitter | clinical testing | The p.Cys778AlafsX34 variant in MSH2 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 778 and leads to a premature termination codon 34 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MSH2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Cys778AlafsX34 variant meets criteria to be classified as likely pathogenic for Lynch syndrome. ACMG/AMP criteria applied: PVS1, PM2. |