ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.552A>C (p.Glu184Asp)

dbSNP: rs63750311
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001857411 SCV002235246 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2022-05-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 184 of the PSEN1 protein (p.Glu184Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 9292884, 12552037, 28323683). ClinVar contains an entry for this variant (Variation ID: 98049). 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 missense change affects PSEN1 function (PMID: 27930341). This variant disrupts the p.Glu184 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been observed in individuals with PSEN1-related conditions (PMID: 22475797), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084336 SCV000116472 not provided not provided no assertion provided not provided

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