Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026562 | SCV001188968 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-04 | criteria provided, single submitter | clinical testing | The p.S252* pathogenic mutation (also known as c.755C>G), located in coding exon 9 of the MLH1 gene, results from a C to G substitution at nucleotide position 755. This changes the amino acid from a serine to a stop codon within coding exon 9. This alteration was identified in a cohort of 1260 individuals undergoing panel testing for Lynch syndrome due to having a diagnosis of a Lynch-associated cancer and/or polyps (Yurgelun MB et al. Gastroenterology 2015 Sep;149:604-13.e20). 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. |
Myriad Genetics, |
RCV003455137 | SCV004189734 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-17 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Invitae | RCV003594086 | SCV004293455 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-05-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 827123). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 25980754). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser252*) 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). |