Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000219633 | SCV000275852 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-22 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.2T>G) is located in coding exon 1 of the PMS2 gene and results from a T to G substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). Other alterations impacting the PMS2 initiation codon have been reported in individuals with early-onset, Lynch syndrome-associated malignancies and tumors demonstrating isolated loss of PMS2 staining by immunohistochemistry (IHC) (Senter et al. Gastroenterology. 2008 Aug;135(2):419-28; Borràs E, J. Med. Genet. 2013 Aug; 50(8):552-63). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV000458145 | SCV000552058 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-05-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 231873). A different variant (c.1A>G) giving rise to the same protein effect has been determined to be pathogenic (PMID: 18602922, 20487569, 23709753). This suggests that this variant is also likely to be causative of disease. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change affects the initiator methionine of the PMS2 mRNA. The next in-frame methionine is located at codon 136. |
Revvity Omics, |
RCV001782709 | SCV002018878 | pathogenic | not provided | 2019-05-06 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000219633 | SCV002530322 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-12 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV003454637 | SCV004187736 | pathogenic | Lynch syndrome 4 | 2023-09-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant is located within the gene translation start codon (p.Met1?) and is predicted to result in abnormal protein translation. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 30680046, 27476653, 18602922]. |