Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507152 | SCV000601416 | likely pathogenic | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587971 | SCV000696191 | likely pathogenic | Lynch syndrome | 2016-09-15 | criteria provided, single submitter | clinical testing | Variant summary: The MLH1 c.927dupC (p.Thr310Hisfs) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.1210_1211delCT/p.Leu404fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121408 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
| Invitae | RCV001389538 | SCV001590931 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr310Hisfs*4) 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 variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 439182). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002376936 | SCV002686526 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-12 | criteria provided, single submitter | clinical testing | The c.927dupC pathogenic mutation, located in coding exon 11 of the MLH1 gene, results from a duplication of C at nucleotide position 927, causing a translational frameshift with a predicted alternate stop codon (p.T310Hfs*4). 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, |
RCV003449445 | SCV004186338 | 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. |
| Baylor Genetics | RCV003449445 | SCV004190607 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-09-10 | criteria provided, single submitter | clinical testing |