Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075308 | SCV000106302 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV000791445 | SCV000543617 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-12-01 | 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 to segregate with Lynch syndrome in a family (PMID: 15655560). ClinVar contains an entry for this variant (Variation ID: 89834). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu557*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002399443 | SCV002709229 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-20 | criteria provided, single submitter | clinical testing | The p.E557* pathogenic mutation (also known as c.1669G>T), located in coding exon 15 of the MLH1 gene, results from a G to T substitution at nucleotide position 1669. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This variant has been reported in a family meeting Amsterdam criteria (Apessos A et al. Br J Cancer, 2005 Jan;92:396-404). 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, |
RCV003455990 | SCV004186469 | 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. |