ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.1148T>G (p.Leu383Trp)

dbSNP: rs1566656647
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000697016 SCV000825606 uncertain significance Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2017-11-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with tryptophan at codon 383 of the PSEN1 protein (p.Leu383Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with autosomal dominant early-onset Alzheimer disease (PMID: 28350801). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determines the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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