Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567028 | SCV000662337 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-02-10 | criteria provided, single submitter | clinical testing | The c.2246_2250delAATTG pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of 5 nucleotides at nucleotide positions 2246 to 2250, causing a translational frameshift with a predicted alternate stop codon (p.E749Gfs*36). 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. |
Invitae | RCV001865719 | SCV002236756 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 479849). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu749Glyfs*36) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). |
Myriad Genetics, |
RCV003451216 | SCV004188957 | 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. |
All of Us Research Program, |
RCV004000862 | SCV004825780 | pathogenic | Lynch syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant deletes 5 nucleotides 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. To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. 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. |