Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076080 | SCV000107095 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing a premature termination codon |
Ambry Genetics | RCV001010574 | SCV001170797 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-22 | criteria provided, single submitter | clinical testing | The p.Q419* pathogenic mutation (also known as c.1255C>T), located in coding exon 7 of the MSH2 gene, results from a C to T substitution at nucleotide position 1255. This changes the amino acid from a glutamine to a stop codon within coding exon 7. This alteration has been detected in multiple individuals who meet either Amsterdam I or Amsterdam II criteria (Miyaki M et al. J. Mol. Med. 1995 Oct;73:515-20; Ikenoue T et al. J Hum Genet. 2019 Dec;64:1187-1194; De Lellis L et al. PLoS One. 2013 Nov;8:e81194; Ben Sghaier R et al. Fam Cancer. 2019 07;18:343-348). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Invitae | RCV001383405 | SCV001582539 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-11-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 90584). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 8581513, 28874130). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln419*) 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). |
Myriad Genetics, |
RCV003452812 | SCV004187989 | pathogenic | Lynch syndrome 1 | 2023-08-01 | 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. |
Baylor Genetics | RCV003452812 | SCV004196858 | pathogenic | Lynch syndrome 1 | 2023-05-03 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000202277 | SCV000257129 | pathogenic | not provided | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000202277 | SCV001740747 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000202277 | SCV001952293 | pathogenic | not provided | no assertion criteria provided | clinical testing |