Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000500713 | SCV000919707 | likely pathogenic | Lynch syndrome | 2017-12-12 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.2425G>T (p.Glu809X) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 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 (e.g. c.2633_2634delAG, p.Glu878fsX3). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 277132 control chromosomes. In addition, one clinical diagnostic laboratory/reputable database classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
| Invitae | RCV001865590 | SCV002231245 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-04-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 433901). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu809*) 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). |
| Ambry Genetics | RCV002446975 | SCV002735204 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-04-25 | criteria provided, single submitter | clinical testing | The p.E809* pathogenic mutation (also known as c.2425G>T), located in coding exon 14 of the MSH2 gene, results from a G to T substitution at nucleotide position 2425. This changes the amino acid from a glutamic acid to a stop codon within coding exon 14. 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, |
RCV003449406 | SCV004186994 | pathogenic | Lynch syndrome 1 | 2023-08-08 | 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 | RCV003449406 | SCV004196894 | likely pathogenic | Lynch syndrome 1 | 2022-10-04 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001353705 | SCV000592548 | pathogenic | not provided | no assertion criteria provided | clinical testing |