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NM_000021.4(PSEN1):c.488A>G (p.His163Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 29, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000534810.6

Allele description [Variation Report for NM_000021.4(PSEN1):c.488A>G (p.His163Arg)]

NM_000021.4(PSEN1):c.488A>G (p.His163Arg)

Gene:
PSEN1:presenilin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.2
Genomic location:
Preferred name:
NM_000021.4(PSEN1):c.488A>G (p.His163Arg)
HGVS:
  • NC_000014.9:g.73186860A>G
  • NG_007386.2:g.55390A>G
  • NM_000021.4:c.488A>GMANE SELECT
  • NM_007318.3:c.476A>G
  • NP_000012.1:p.His163Arg
  • NP_015557.2:p.His159Arg
  • LRG_224t1:c.488A>G
  • LRG_224:g.55390A>G
  • LRG_224p1:p.His163Arg
  • NC_000014.8:g.73653568A>G
  • NM_000021.3:c.488A>G
  • P49768:p.His163Arg
Protein change:
H159R; HIS163ARG
Links:
UniProtKB: P49768#VAR_006428; OMIM: 104311.0002; dbSNP: rs63750590
NCBI 1000 Genomes Browser:
rs63750590
Molecular consequence:
  • NM_000021.4:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007318.3:c.476A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Alzheimer disease 3 (AD3)
Synonyms:
Alzheimer disease early onset type 3; ALZHEIMER DISEASE, FAMILIAL, 3
Identifiers:
MONDO: MONDO:0011913; MedGen: C1843013; Orphanet: 1020; OMIM: 607822
Name:
Frontotemporal dementia (FTD)
Synonyms:
FRONTOTEMPORAL LOBE DEMENTIA; WILHELMSEN-LYNCH DISEASE; Dementia, frontotemporal, with parkinsonism; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0017276; MedGen: C0338451; Orphanet: 282; OMIM: 600274; Human Phenotype Ontology: HP:0002145
Name:
Pick disease
Synonyms:
PICK DISEASE OF BRAIN; LOBAR ATROPHY OF BRAIN; Pick's disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008243; MedGen: C0236642; Orphanet: 282; OMIM: 172700
Name:
Acne inversa, familial, 3 (ACNINV3)
Identifiers:
MONDO: MONDO:0013398; MedGen: C3151038; OMIM: 613737

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000639607Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 29, 2021) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, et al.

Nature. 1995 Jun 29;375(6534):754-60.

PubMed [citation]
PMID:
7596406

Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.

Kamino K, Sato S, Sakaki Y, Yoshiiwa A, Nishiwaki Y, Takeda M, Tanabe H, Nishimura T, Ii K, St George-Hyslop PH, Miki T, Ogihara T.

Neurosci Lett. 1996 Apr 26;208(3):195-8.

PubMed [citation]
PMID:
8733303
See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000639607.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This missense change has been observed in individual(s) with early-onset Alzheimer's disease (EOAD) (PMID: 7596406, 8733303, 12433263, 22503161, 26337232, 27264813). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 163 of the PSEN1 protein (p.His163Arg). ClinVar contains an entry for this variant (Variation ID: 18124). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 8986743, 19111578, 22461631). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PSEN1 protein function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024