Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075183 | SCV000106174 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001059158 | SCV001223770 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-04-20 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual affected with Lynch syndrome (PMID: 17653898). This variant is also known as c.1377_1378insA in the literature. ClinVar contains an entry for this variant (Variation ID: 89709). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu460Argfs*19) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002381379 | SCV002699515 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-02-27 | criteria provided, single submitter | clinical testing | The c.1377dupA pathogenic mutation, located in coding exon 12 of the MLH1 gene, results from a duplication of A at nucleotide position 1377, causing a translational frameshift with a predicted alternate stop codon (p.E460Rfs*19). This alteration has been detected in the germline of someone diagnosed with colorectal or endometrial cancer showing the loss of MLH1 and PMS2 on immunohistochemistry (Rahner N et al. Acta Oncol, 2007;46:763-9). 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, |
RCV003451021 | SCV004189935 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-20 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |