Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657313 | SCV000779044 | pathogenic | not provided | 2017-04-12 | criteria provided, single submitter | clinical testing | This combined deletion and insertion is denoted MSH2 c.2045_2047delCTGinsTT at the cDNA level and p.Thr682IlefsX3 (T682IfsX3) at the protein level. The surrounding sequence is CAAA[delCTG][insTT]GGGT. The variant causes a frameshift which changes a Threonine to an Isoleucine at codon 682, and creates a premature stop codon at position 3 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Labcorp Genetics |
RCV001241454 | SCV001414471 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-06-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr682Ilefs*3) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related conditions. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003451589 | SCV004187869 | pathogenic | Lynch syndrome 1 | 2023-08-07 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Ambry Genetics | RCV004025997 | SCV005033580 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-21 | criteria provided, single submitter | clinical testing | The c.2045_2047delCTGinsTT pathogenic mutation, located in coding exon 13 of the MSH2 gene, results from the deletion of 3 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.T682Ifs*3). 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. |