Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075703 | SCV000106706 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002326787 | SCV002629488 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-28 | criteria provided, single submitter | clinical testing | The c.420delA pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 420, causing a translational frameshift with a predicted alternate stop codon (p.K140Nfs*20). This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated loss of MLH1 and PMS2 expression by immunohistochemistry (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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, |
RCV003451147 | SCV004189812 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Invitae | RCV003593886 | SCV004293449 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-01-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys140Asnfs*20) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 90214). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary nonpolyposis colorectal cancer (PMID: 10874307). This variant is not present in population databases (gnomAD no frequency). |