ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.415A>G (p.Met139Val)

dbSNP: rs63751037
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000084304 SCV000843418 pathogenic not provided 2015-12-24 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000084304 SCV001248745 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000084304 SCV001446922 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000019756 SCV002764843 pathogenic Alzheimer disease 3 2022-07-29 criteria provided, single submitter clinical testing
Invitae RCV003764610 SCV004570949 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 139 of the PSEN1 protein (p.Met139Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with early-onset familial Alzheimer disease (PMID: 7550356). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 18128). 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 not expected to disrupt PSEN1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019756 SCV000040054 pathogenic Alzheimer disease 3 2003-06-01 no assertion criteria provided literature only
GeneReviews RCV000019756 SCV000040385 not provided Alzheimer disease 3 no assertion provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084304 SCV000116440 not provided not provided no assertion provided not provided

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