Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075894 | SCV000106910 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV002371908 | SCV002684432 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-06-03 | criteria provided, single submitter | clinical testing | The c.866_867delAC pathogenic mutation, located in coding exon 10 of the MLH1 gene, results from a deletion of two nucleotides at nucleotide positions 866 to 867, causing a translational frameshift with a predicted alternate stop codon (p.H289Pfs*17). This alteration was identified in one family from Norway that met Amsterdam I and/or II criteria (Sjursen W et al. J. Med. Genet., 2010 Sep;47:579-85). In addition to the clinical data presented in the literature, 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, |
RCV003452778 | SCV004186195 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Invitae | RCV003593890 | SCV004293458 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-08-23 | 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.His289Profs*17) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 20587412). ClinVar contains an entry for this variant (Variation ID: 90401). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
| Laboratory for Genotyping Development, |
RCV003162490 | SCV002758375 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |