Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025765 | SCV001188017 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-31 | criteria provided, single submitter | clinical testing | The p.E230* pathogenic mutation (also known as c.688G>T), located in coding exon 9 of the MLH1 gene, results from a G to T substitution at nucleotide position 688. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation was detected in 1/436 French colorectal cancer probands; however clinical information was not provided for this individual (Parc Y et al. J. Med. Genet., 2003 Mar;40:208-13). In addition to the clinical data presented in the literature, 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. |
| Color Diagnostics, |
RCV001025765 | SCV001346674 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-10-07 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 9 of the MLH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in 1 individual affected with gastric cancer (PMID: 29882764). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MLH1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. |
| Invitae | RCV001873399 | SCV002230227 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-12-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu230*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 826682). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 12624141). This variant is not present in population databases (gnomAD no frequency). |