ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.401T>G (p.Leu134Arg) (rs1595002439)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823608 SCV000964473 uncertain significance Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-10-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 134 of the PSEN1 protein (p.Leu134Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with early onset Alzheimer disease (PMID: 22503161, Invitae). Experimental studies have shown that this missense change results in decreased Abeta40 and Abeta42 peptide production by the gamma-secretase protein (PMID: 27930341). 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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