Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000234014 | SCV000284062 | pathogenic | Lynch syndrome | 2016-01-16 | criteria provided, single submitter | clinical testing | This sequence change inserts 1 nucleotide in exon 1 of the MLH1 mRNA (c.38dupA), causing a frameshift at codon 14. This creates a premature translational stop signal (p.Thr14Aspfs*17) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic. |
Invitae | RCV001380004 | SCV001577925 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr14Aspfs*17) 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 has not been reported in the literature in individuals affected with MLH1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 237338). |
Ambry Genetics | RCV002365174 | SCV002623693 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-06 | criteria provided, single submitter | clinical testing | The c.38dupA pathogenic mutation, located in coding exon 1 of the MLH1 gene, results from a duplication of A at nucleotide position 38, causing a translational frameshift with a predicted alternate stop codon. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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, |
RCV003456010 | SCV004186454 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |