Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001180218 | SCV001345088 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-09 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 1 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. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been observed in three suspected Lynch syndrome families, with one proband affected with colon cancer and sebaceous carcinoma before age 50 (PMID: 26437257, 28874130). 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. Based on available evidence, this variant is classified as Pathogenic. |
| Invitae | RCV001875977 | SCV002242811 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-06-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Lynch syndrome (PMID: 21681552, 28874130). ClinVar contains an entry for this variant (Variation ID: 921072). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys59Glnfs*23) 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). |
| Mendelics | RCV002249760 | SCV002517632 | pathogenic | Lynch syndrome 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001180218 | SCV002711632 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-10-05 | criteria provided, single submitter | clinical testing | The c.174dupC pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a duplication of C at nucleotide position 174, causing a translational frameshift with a predicted alternate stop codon (p.K59Qfs*23). This alteration has been reported in Brazilian families meeting Bethesda or Amsterdam criteria and has been referred to as c.175dup in published literature (Valentin MD et al. Fam. Cancer, 2011 Dec;10:641-7; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2013 Dec;11:18). 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. |