Submissions for variant NM_000021.4(PSEN1):c.796G>A (p.Gly266Ser)

dbSNP: rs121917807

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003388569	SCV004100378	likely pathogenic	Alzheimer disease 3		criteria provided, single submitter	clinical testing	The missense variant p.G266S in PSEN1 (NM_000021.4) has been reported treported previously in a Japanese family where it segregated amongst affected members who were affected with Alzheimer with spastic paraparesis and apraxia (Tsutsui MM et al). The variant has been submitted to ClinVar as Pathogenic based on the above publication. It is present in a hotspot region with mutations affecting the neighbouring residues (Tsuitsui MM et al). The p.G266S variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes.The p.G266S missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 266 of PSEN1 is conserved in all mammalian species. The nucleotide c.796 in PSEN1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM	RCV000019774	SCV000040072	pathogenic	Alzheimer disease, familial, 3, with spastic paraparesis and apraxia	2002-04-08	no assertion criteria provided	literature only