ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1593_1610dup (p.His532_Glu537dup) (rs587780043)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228238 SCV000285079 uncertain significance Lynch syndrome 2015-12-01 criteria provided, single submitter clinical testing This sequence change inserts 18 nucleotides in exon 11 of the PMS2 mRNA (c.1593_1610dup). This leads to the insertion of 6 amino acid residues in the PMS2 protein (p.His532_Glu537dup) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. However, ClinVar contains an entry for this variant (Variation ID: 127764). This insertion change is not located within any functionally conserved domain of the PMS2 protein (PMID: 17230503) and the duplicated residues are not well conserved throughout evolution. In summary, this variant causes amino acid residues insertion into a region that does not contain known functional domains. Although there is no evidence to suggest that this change affects protein function or causes disease, the evidence available at this time is insufficient to prove that conclusively. For these reasons, this change has been classified as a Variant of Uncertain Significance.
Invitae RCV000547678 SCV000625542 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-07 criteria provided, single submitter clinical testing This variant, c.1593_1610dup, results in the insertion of 6 amino acids to the PMS2 protein (p.His532_Glu537dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 127764). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573191 SCV000663548 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-20 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000573191 SCV000691031 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing
Mendelics RCV000228238 SCV000838175 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761031 SCV000890946 uncertain significance T Lymphoblastic Leukemia/Lymphoma 2016-04-11 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.