Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075694 | SCV000106698 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002354261 | SCV002620931 | pathogenic | Hereditary cancer-predisposing syndrome | 2014-12-13 | criteria provided, single submitter | clinical testing | The c.389delA pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 389, causing a translational frameshift with a predicted alternate stop codonp (T130Sfs*6). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
Myriad Genetics, |
RCV003451144 | SCV004186575 | 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 | RCV003593885 | SCV004364991 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr130Serfs*6) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 90206). For these reasons, this variant has been classified as Pathogenic. |