Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075312 | SCV000106306 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV000703498 | SCV000832401 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-08-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr561*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. 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 hereditary nonpolyposis colorectal cancer (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 89838). This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV001012704 | SCV001173190 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-02-21 | criteria provided, single submitter | clinical testing | The p.Y561* pathogenic mutation (also known as c.1683C>G), located in coding exon 15 of the MLH1 gene, results from a C to G substitution at nucleotide position 1683. This changes the amino acid from a tyrosine to a stop codon within coding exon 15. In a study of 1,721 German probands suspected of HNPCC, this mutation was detected in 1 family. (Mangold E et al. Int. J. Cancer, 2005 Sep;116:692-702). 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. |
Myriad Genetics, |
RCV003451050 | SCV004186350 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-21 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |