Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076144 | SCV000107165 | pathogenic | Lynch syndrome 1 | 2014-10-10 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability >0.99 |
| Genome |
RCV000509472 | SCV000607327 | not provided | Hereditary nonpolyposis colorectal neoplasms | no assertion provided | phenotyping only | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
| Department of Pathology and Laboratory Medicine, |
RCV000509472 | SCV001553258 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-05-29 | no assertion criteria provided | clinical testing | The MSH2 c.1387-9T>A variant was not in the literature. The c.1387-9T>A variant was identified in dbSNP (ID: rs587779087) and ClinVar (classified as pathogenic in association with Hereditary nonpolyposis colorectal neoplasms and Lynch syndrome 1). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (November 01, 2023, v4.0). The c.1387-9T>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. The variant occurs inside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) predict a deleterious effect on splicing. However, this information is not predictive enough to assume pathogenicity. The c.1387-9T>A variant was identified in an individual from our laboratory with a diagnosis of HNPCC. This intronic substitution was examined by RT-PCR analysis and found to cause an alternate transcript that was predicted to result in a frameshift and to create a premature stop codon. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |