Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076747 | SCV000107784 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Counsyl | RCV000412047 | SCV000488312 | pathogenic | Lynch syndrome 1 | 2016-02-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001224865 | SCV001397091 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-23 | 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: 91242). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 14594944, 28449805, 28874130). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu302*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). |
Ambry Genetics | RCV002444542 | SCV002682890 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | The p.L302* pathogenic mutation (also known as c.905T>A), located in coding exon 5 of the MSH2 gene, results from a T to A substitution at nucleotide position 905. This changes the amino acid from a leucine to a stop codon within coding exon 5. This alteration has been reported in Lynch syndrome patients whose personal and family cancer histories satisfy Amsterdam II criteria (Tomita N et al. Jpn. J. Clin. Oncol., 2003 Sep;33:486-9; Cruz-Correa M et al. Fam. Cancer, 2015 Sep;14:415-25). 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, |
RCV000412047 | SCV004018345 | pathogenic | Lynch syndrome 1 | 2023-03-21 | 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. |