ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.697A>G (p.Met233Val) (rs63751287)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000712874 SCV000843421 likely pathogenic not provided 2018-06-13 criteria provided, single submitter clinical testing
GeneReviews RCV000020086 SCV000040389 pathologic Alzheimer disease, type 3 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000818883 SCV000959520 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 233 of the PSEN1 protein (p.Met233Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with early-onset Alzheimer’s disease in a family (PMID: 29316780) and has also been reported in additional unrelated, affected individuals (PMID:11684347). ClinVar contains an entry for this variant (Variation ID: 21028). Experimental studies have shown that this missense change impairs the cleavage activity of the presenilin-1 protein (PMID: 27014058). The observation of one or more missense substitutions at this codon (p.Met233Thr, p.Met233Leu, p.Met233Ile) in affected individuals suggests that this may be a clinically significant residue (PMID: 10533070, 11524469, 16948293, 18667258, 28350801). For these reasons, this variant has been classified as Pathogenic.

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