Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075396 | SCV000106390 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000571618 | SCV000676069 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-11-14 | criteria provided, single submitter | clinical testing | The c.1877delT pathogenic mutation, located in coding exon 16 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1877, causing a translational frameshift with a predicted alternate stop codon (p.F626Sfs*11). This mutation has been detected in a patient diagnosed with colorectal cancer at age 40y who reported a family history of early-onset colorectal and endometrial cancer (Samowitz WS et al. Gastroenterology. 2001 Oct;121(4):830-8). 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. |
Invitae | RCV000692128 | SCV000819937 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-03-12 | criteria provided, single submitter | clinical testing | 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 has been observed in an individual affected with colon cancer (PMID: 11606497). ClinVar contains an entry for this variant (Variation ID: 89917). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe626Serfs*11) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
Myriad Genetics, |
RCV003451076 | SCV004186312 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-24 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |