ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.1184A>T (p.Lys395Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV002474302 SCV002770799 uncertain significance not provided 2021-09-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002569397 SCV003217048 uncertain significance Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-02-10 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 395 of the PSEN1 protein (p.Lys395Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PSEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1806873). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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