ClinVar Miner

Submissions for variant NM_004621.6(TRPC6):c.2689G>A (p.Glu897Lys)

dbSNP: rs121434395
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
Ambry Genetics RCV003362661 SCV004084527 likely pathogenic Inborn genetic diseases 2023-08-21 criteria provided, single submitter clinical testing The c.2689G>A (p.E897K) alteration is located in exon 13 (coding exon 13) of the TRPC6 gene. This alteration results from a G to A substitution at nucleotide position 2689, causing the glutamic acid (E) at amino acid position 897 to be replaced by a lysine (K). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been identified in multiple individuals with clinical features consistent with TRPC6-related focal segmental glomerulosclerosis (Reiser, 2005; Groopman, 2019; Lu, 2022). This amino acid position is highly conserved in available vertebrate species. Based on internal structural analysis, E897K is more disruptive to the CH2 domain of TRPC6 than our internal threshold for deleterious destabilization, though there are no comparable internally pathogenic variants nearby for comparison (Tang, 2018; Guo, 2022). Functional studies show that E897K leads to altered protein function (Reiser, 2005; Riehle, 2016; Polat, 2019; Schlöndorff, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
OMIM RCV000006531 SCV000026714 pathogenic Focal segmental glomerulosclerosis 2 2005-07-01 no assertion criteria provided literature only
Gharavi Laboratory, Columbia University RCV000681807 SCV000809278 pathogenic not provided 2018-09-16 no assertion criteria provided research

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.