Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076303 | SCV000107324 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Invitae | RCV000688460 | SCV000816072 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-08-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been observed in several individuals affected with Lynch syndrome (PMID: 8613431, 11754112, 15849733, 19723918). ClinVar contains an entry for this variant (Variation ID: 90802). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr619*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002408598 | SCV002721872 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-05-08 | criteria provided, single submitter | clinical testing | The p.Y619* pathogenic mutation (also known as c.1857T>G), located in coding exon 12 of the MSH2 gene, results from a T to G substitution at nucleotide position 1857. This changes the amino acid from a tyrosine to a stop codon within coding exon 12. This alteration was first reported in a Japanese kindred that met Amsterdam criteria for Lynch syndrome (Lu SL et al. Jpn. J. Cancer Res., 1996 Mar;87:279-87; Bai YQ et al. Int. J. Cancer, 1999 Aug;82:512-5). This alteration was also reported by a German group in an individual diagnosed with MSI-H colon cancer at 45 that displayed absent MSH2 staining on immunohistochemistry (IHC) and family history met Amsterdam I criteria for Lynch syndrome (Krüger S et al. Hum. Mutat., 2002 Jan;19:82). 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, |
RCV003452862 | SCV004186992 | pathogenic | Lynch syndrome 1 | 2023-08-03 | 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. |