Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000204356 | SCV000259610 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gly250*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 219627). |
| Ambry Genetics | RCV000490946 | SCV000580479 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-07 | criteria provided, single submitter | clinical testing | The p.G250* pathogenic mutation (also known as c.748G>T), located in coding exon 4 of the MSH2 gene, results from a G to T substitution at nucleotide position 748. This changes the amino acid from a glycine to a stop codon within coding exon 4. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001527063 | SCV001737903 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2021-06-15 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.748G>T (p.Gly250X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251418 control chromosomes. To our knowledge, no occurrence of c.748G>T in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Myriad Genetics, |
RCV003454540 | SCV004188156 | pathogenic | Lynch syndrome 1 | 2023-07-27 | 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. |
| Baylor Genetics | RCV003454540 | SCV004196856 | likely pathogenic | Lynch syndrome 1 | 2023-05-05 | criteria provided, single submitter | clinical testing |