Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004018570 | SCV002683468 | uncertain significance | not specified | 2020-09-11 | criteria provided, single submitter | clinical testing | The c.885delG variant, located in coding exon 1 of the MLH3 gene, results from a deletion of one nucleotide at nucleotide position 885, causing a translational frameshift with a predicted alternate stop codon (p.H296Tfs*12). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, the gene-disease association for MLH3 is limited. This variant was identified in one of 70 families suspected of hereditary colon cancer and negative for MLH1, MSH2, and MSH6 germline mutations; this variant was absent in 96 healthy controls (Liu HX et al. Cancer Res., 2003 Apr;63:1894-9). The c.885del variant was identified in one of 274 individuals meeting Amsterdam criteria and/or revised Bethesda guidelines but did not segregate with disease in this family (Hansen MF et al. Clin. Genet., 2017 Oct;92:405-414). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000005903 | SCV004278786 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 7 | 2023-08-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 5563). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 12702580, 31297992). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.His296Thrfs*12) in the MLH3 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MLH3 cause disease. |
| OMIM | RCV000005903 | SCV000026085 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 7 | 2003-04-15 | no assertion criteria provided | literature only | |
| OMIM | RCV000005904 | SCV000026086 | pathogenic | Endometrial cancer | 2003-04-15 | no assertion criteria provided | literature only |