Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076199 | SCV000107216 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Gene |
RCV000479550 | SCV000568630 | pathogenic | not provided | 2016-12-06 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in MSH2 is denoted c.1576delA at the cDNA level and p.Thr526ProfsX17 (T526PfsX17) at the protein level. The normal sequence, with the base that is deleted in brackets, is TGTA[delA]CCTG. The deletion causes a frameshift which changes a Threonine to a Proline at codon 526, and creates a premature stop codon at position 17 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT) classifies this variant as pathogenic (Thompson 2014). MSH2 c.1576delA has been reported in patients with Muir-Torre syndrome and Lynch syndrome (Kruse 1998, Bonadona 2011, Kovac 2011, Limburg 2011). We consider this variant to be pathogenic. |
Invitae | RCV001230571 | SCV001403055 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-03-16 | 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: 90702). This premature translational stop signal has been observed in individuals with Lynch syndrome (PMID: 9634524, 21056691, 21671081). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr526Profs*17) 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 | RCV002399453 | SCV002704123 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-07-06 | criteria provided, single submitter | clinical testing | The c.1576delA pathogenic mutation, located in coding exon 10 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1576, causing a translational frameshift with a predicted alternate stop codon (p.T526Pfs*17). This alteration has been identified in multiple individuals with colorectal and/or endometrial cancer (Kruse R et al. Am. J. Hum. Genet., 1998 Jul;63:63-70; Kovac M et al. Fam. Cancer, 2011 Sep;10:605-16; Limburg PJ et al. Clin. Gastroenterol. Hepatol., 2011 Jun;9:497-50). 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, |
RCV003452842 | SCV004188076 | pathogenic | Lynch syndrome 1 | 2023-08-02 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |