ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.659G>A (p.Arg220Gln)

gnomAD frequency: 0.00001  dbSNP: rs763831389
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803782 SCV000943668 uncertain significance Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-03-25 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PSEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 648949). This missense change has been observed in individual(s) with clinical features of PSEN1-related conditions (Invitae). This variant is present in population databases (rs763831389, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 220 of the PSEN1 protein (p.Arg220Gln).
PreventionGenetics, part of Exact Sciences RCV003411770 SCV004106429 uncertain significance PSEN1-related disorder 2022-08-30 criteria provided, single submitter clinical testing The PSEN1 c.659G>A variant is predicted to result in the amino acid substitution p.Arg220Gln. To our knowledge, this variant has not been reported in the literature, although an alternate substitution impacting the same amino acid (p.Arg220Pro, described as R220P) was reported in a case of familial late-onset Alzheimer's disease (Piccoli et al. 2016. PubMed ID: 26925509).The c.659G>A (p.Arg220Gln) variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-73659462-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.