Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204170 | SCV001375365 | pathogenic | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2019-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 271 of the PSEN1 protein (p.Leu271Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Alzheimer's disease in a family (PMID: 12493737). ClinVar contains an entry for this variant (Variation ID: 18148). This variant has been reported to affect PSEN1 protein function (PMID: 12493737, 27930341). For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV002051789 | SCV002318537 | pathogenic | Alzheimer disease 3 | 2022-03-22 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PSEN1 related disorder (ClinVar ID: VCV000018148, PMID:12493737). The variant was co-segregated with Alzheimer disease, type 3, with spastic paraparesis and unusual plaques in multiple affected family members (PMID: 12493737). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 12493737). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94>=0.6, 3CNET: 0.883>=0.75). A missense variant is a common mechanism . It is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV000019778 | SCV000040076 | pathogenic | Alzheimer disease, familial, 3, with unusual plaques | 2003-02-28 | no assertion criteria provided | literature only | |
| VIB Department of Molecular Genetics, |
RCV000084375 | SCV000116511 | not provided | not provided | no assertion provided | not provided | ||
| Codex Genetics Limited | RCV000984888 | SCV000995997 | pathogenic | Alzheimer disease 3; Spastic paraparesis | 2019-02-28 | no assertion criteria provided | provider interpretation |