Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000808710 | SCV000948825 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-08-07 | 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 not been reported in the literature in individuals with MLH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu671Glyfs*4) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002422776 | SCV002724283 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-24 | criteria provided, single submitter | clinical testing | The c.2009dupA pathogenic mutation, located in coding exon 18 of the MLH1 gene, results from a duplication of A at nucleotide position 2009, causing a translational frameshift with a predicted alternate stop codon (p.E671Gfs*4). 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. |