ClinVar Miner

Submissions for variant NM_000534.5(PMS1):c.1888C>T (p.Arg630Ter)

gnomAD frequency: 0.00009  dbSNP: rs139932286
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV003460857 SCV004205331 uncertain significance PMS1-related breast cancer 2023-09-28 criteria provided, single submitter clinical testing
ITMI RCV000121832 SCV000086030 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355189 SCV001549999 uncertain significance not provided no assertion criteria provided clinical testing The PMS1 p.Arg630* variant was identified in the literature in a female patient with uveal melanoma, congenital bilateral nevus of Ota and ocular surface melanosis (Toomey_2019_PMID:31367589). The variant was identified in dbSNP (ID: rs139932286) and ClinVar (submitted by ITMI, classification not provided). The variant was identified in control databases in 38 of 266820 chromosomes at a frequency of 0.0001424 (Genome Aggregation Database March 6, 2019, v2.1.1, non-cancer). The variant was observed in the following populations: Ashkenazi Jewish in 22 of 9822 chromosomes (freq: 0.00224), Latino in 5 of 35036 chromosomes (freq: 0.000143), South Asian in 3 of 30488 chromosomes (freq: 0.000098) and European (non-Finnish) in 8 of 117296 chromosomes (freq: 0.000068), but was not observed in the African, East Asian, European (Finnish), or Other populations. The c.1888C>T variant leads to a premature stop codon at position 630 which is predicted to lead to a truncated or absent protein and loss of function. However, the role of loss of function PMS1 variants in disease is not currently well established. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.