ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.437T>C (p.Met146Thr)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701153 SCV005204717 likely pathogenic Alzheimer disease 3 2024-06-18 criteria provided, single submitter clinical testing Variant summary: PSEN1 c.437T>C (p.Met146Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251472 control chromosomes. To our knowledge, no occurrence of c.437T>C in individuals affected with Alzheimer Disease, Type 3 and no experimental evidence demonstrating its impact on protein function have been reported. However, multiple variants affecting the same codon (e.g. Met146Ile, Met146Val, Met146Leu) have been reported in affected individuals and have been classified as pathogenic in ClinVar, indicating the critical relevance of codon 146 to PSEN1 function. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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.