ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.530T>C (p.Phe177Ser)

dbSNP: rs63749806
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002513898 SCV003442901 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 177 of the PSEN1 protein (p.Phe177Ser). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe177 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been observed in individuals with PSEN1-related conditions (PMID: 22810102, 34776449), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 15004326). 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: 98047). This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 15004326, 23850332). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
VIB Department of Molecular Genetics, University of Antwerp RCV000084333 SCV000116469 not provided not provided no assertion provided not provided

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