ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.338T>C (p.Leu113Pro) (rs63751399)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000084292 SCV001145224 likely pathogenic not provided 2019-04-04 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282660 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Damaging to protein function(s) relevant to disease mechanism.
Invitae RCV001228362 SCV001400758 likely pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2019-10-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 113 of the PSEN1 protein (p.Leu113Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual and a family affected with clinical features of early-onset Alzheimer's disease (PMID: 11094121, Invitae). This gene is also known as PS1 in the literature. ClinVar contains an entry for this variant (Variation ID: 18145). This variant has been reported not to substantially affect PSEN1 protein function (PMID: 17431506, 20634584). This variant disrupts the p.Leu113 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been observed in individuals with PSEN1-related conditions (PMID: 15776278), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000019775 SCV000040073 pathogenic Frontotemporal dementia 2000-11-28 no assertion criteria provided literature only
GeneReviews RCV000020084 SCV000040384 pathologic Alzheimer disease, type 3 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084292 SCV000116428 not provided not provided no assertion provided not provided

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