ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.104G>A (p.Arg35Gln) (rs63750592)

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
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172094 SCV000054832 uncertain significance Alzheimer disease 2013-06-24 criteria provided, single submitter research
Invitae RCV000640608 SCV000762202 uncertain significance Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 35 of the PSEN1 protein (p.Arg35Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs63750592, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in several individuals affected with Alzheimer disease and dementia (PMID: 11524469, 23990795, 26242991) and has also been reported in an unaffected control (PMID: 18667258). ClinVar contains an entry for this variant (Variation ID: 98004). Experimental studies have shown that this missense change reduces the secretase activity of the PSEN1 protein, but does not produce a significantly higher ratio of long amyloid precursor proteins (AB42) which is typically associated with Alzheimer disease (PMID: 27930341). 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.
Illumina Clinical Services Laboratory,Illumina RCV001120057 SCV001278520 likely benign Cardiomyopathy, dilated, 1u 2017-09-12 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001120058 SCV001278521 uncertain significance Alzheimer disease, type 3 2017-09-12 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
VIB Department of Molecular Genetics, University of Antwerp RCV000084280 SCV000116416 not provided not provided no assertion provided not provided

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.