ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.791C>T (p.Pro264Leu)

dbSNP: rs63750301
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000415376 SCV000493061 likely pathogenic Mental deterioration; Dementia 2015-02-06 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000084370 SCV000843422 pathogenic not provided 2018-06-05 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000084370 SCV001447788 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV001387954 SCV001588727 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-08-24 criteria provided, single submitter clinical testing This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 8634712, 16033913, 28350801). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs63750301, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 264 of the PSEN1 protein (p.Pro264Leu). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 11959395, 26438723). 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 expected to disrupt PSEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 98080).
CeGaT Center for Human Genetics Tuebingen RCV000084370 SCV004184412 pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing PSEN1: PM2, PM5, PS3:Moderate, PS4:Moderate, PP3, PP4
VIB Department of Molecular Genetics, University of Antwerp RCV000084370 SCV000116506 not provided not provided no assertion provided not provided

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