Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075112 | SCV000106103 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002426629 | SCV002742581 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-18 | criteria provided, single submitter | clinical testing | The c.1101delC pathogenic mutation, located in coding exon 12 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1101, causing a translational frameshift with a predicted alternate stop codon (p.S368Rfs*33). This mutation has been identified in a high-risk CRC family (Terdiman JP et al. Gastroenterology, 2001 Jan;120:21-30). In addition to the published data, 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 | RCV002514336 | SCV003525418 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-02-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89642). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 11208710). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser368Argfs*33) 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). |
Myriad Genetics, |
RCV003451005 | SCV004187625 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-19 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |