Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075670 | SCV000106672 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding variation introducing premature termination codon |
Gene |
RCV000485841 | SCV000570936 | pathogenic | not provided | 2016-07-11 | criteria provided, single submitter | clinical testing | This deletion of two nucleotides in MLH1 is denoted c.372_373delTG at the cDNA level and p.Ala125IlefsX15 (A125IfsX15) at the protein level. The normal sequence, with the bases that are deleted in braces, is AGTG[TG]CATA. The deletion causes a frameshift which changes an Alanine to an Isoleucine at codon 125, and creates a premature stop codon at position 15 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
Myriad Genetics, |
RCV003451137 | SCV004186401 | 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 | RCV003593884 | SCV004273542 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-07-20 | 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: 90182). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala125Ilefs*15) 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). |