ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.791C>T (p.Pro264Leu) (rs63750301)

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Total submissions: 5
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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, type 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2020-08-25 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 264 of the PSEN1 protein (p.Pro264Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with early-onset Alzheimer disease (PMID: 8634712, 16033913, 28350801). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98080). 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. Experimental studies have shown that this variant affects PSEN1 protein function (PMID: 11959395, 26438723). For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084370 SCV000116506 not provided not provided no assertion provided not provided

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