ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1981G>T (p.Glu661Ter)

dbSNP: rs778531080
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165222 SCV000215936 pathogenic Hereditary cancer-predisposing syndrome 2017-11-10 criteria provided, single submitter clinical testing The p.E661* pathogenic mutation (also known as c.1981G>T), located in coding exon 11 of the PMS2 gene, results from a G to T substitution at nucleotide position 1981. This changes the amino acid from a glutamic acid to a stop codon within coding exon 11. This mutation was observed in two individuals diagnosed with colon cancer in their 30's and tumor studies for both individuals showed isolated loss of PMS2 protein on IHC (Gulati, S et al. Gastrointest Cancer Res. 2011 Sep;4(5-6):188-90; Vaughn, CP et al. Hum Mutat. 2010 May;31(5):588-93). One of the tumors was also found to be MSI-High (Gulati, S et al. Gastrointest Cancer Res. 2011 Sep;4(5-6):188-90). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001201579 SCV001372655 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu661*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 20205264, 22295133, 28514183). ClinVar contains an entry for this variant (Variation ID: 185743). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003454403 SCV004187690 pathogenic Lynch syndrome 4 2023-09-21 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.
Baylor Genetics RCV003454403 SCV004207900 pathogenic Lynch syndrome 4 2022-04-14 criteria provided, single submitter clinical testing
GeneDx RCV004721281 SCV005326984 pathogenic not provided 2024-03-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 24362816, 21376568, 28514183, 20205264, 22295133, 25691505)

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.