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NM_000484.4(APP):c.2077G>C (p.Glu693Gln) AND Alzheimer disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 2, 2020
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:
RCV001386879.7

Allele description [Variation Report for NM_000484.4(APP):c.2077G>C (p.Glu693Gln)]

NM_000484.4(APP):c.2077G>C (p.Glu693Gln)

Gene:
APP:amyloid beta precursor protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q21.3
Genomic location:
Preferred name:
NM_000484.4(APP):c.2077G>C (p.Glu693Gln)
HGVS:
  • NC_000021.9:g.25891856C>G
  • NG_007376.2:g.284273G>C
  • NM_000484.4:c.2077G>CMANE SELECT
  • NM_001136016.3:c.2005G>C
  • NM_001136129.3:c.1684G>C
  • NM_001136130.3:c.1909G>C
  • NM_001136131.3:c.1747G>C
  • NM_001204301.2:c.2023G>C
  • NM_001204302.2:c.1966G>C
  • NM_001204303.2:c.1798G>C
  • NM_001385253.1:c.1909G>C
  • NM_201413.3:c.2020G>C
  • NM_201414.3:c.1852G>C
  • NP_000475.1:p.Glu693Gln
  • NP_001129488.1:p.Glu669Gln
  • NP_001129601.1:p.Glu562Gln
  • NP_001129602.1:p.Glu637Gln
  • NP_001129603.1:p.Glu583Gln
  • NP_001191230.1:p.Glu675Gln
  • NP_001191231.1:p.Glu656Gln
  • NP_001191232.1:p.Glu600Gln
  • NP_001372182.1:p.Glu637Gln
  • NP_958816.1:p.Glu674Gln
  • NP_958817.1:p.Glu618Gln
  • NC_000021.8:g.27264168C>G
  • NM_000484.3:c.2077G>C
  • P05067:p.Glu693Gln
Protein change:
E562Q; GLU693GLN
Links:
UniProtKB: P05067#VAR_000017; OMIM: 104760.0001; dbSNP: rs63750579
NCBI 1000 Genomes Browser:
rs63750579
Molecular consequence:
  • NM_000484.4:c.2077G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136016.3:c.2005G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136129.3:c.1684G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136130.3:c.1909G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136131.3:c.1747G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204301.2:c.2023G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204302.2:c.1966G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204303.2:c.1798G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385253.1:c.1909G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201413.3:c.2020G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201414.3:c.1852G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Alzheimer disease
Synonyms:
Presenile and senile dementia; Alzheimer's disease
Identifiers:
MONDO: MONDO:0004975; MeSH: D000544; MedGen: C0002395; Orphanet: 1020; Human Phenotype Ontology: HP:0002511

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001587274Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 2, 2020) 		germlineclinical testing

PubMed (8)
[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

Dutch and Arctic mutant peptides of beta amyloid(1-40) differentially affect the FGF-2 pathway in brain endothelium.

Solito R, Corti F, Fossati S, Mezhericher E, Donnini S, Ghiso J, Giachetti A, Rostagno A, Ziche M.

Exp Cell Res. 2009 Feb 1;315(3):385-95. doi: 10.1016/j.yexcr.2008.11.002. Epub 2008 Nov 19.

PubMed [citation]
PMID:
19061884
PMCID:
PMC2764262

Pathogenic effects of D23N Iowa mutant amyloid beta -protein.

Van Nostrand WE, Melchor JP, Cho HS, Greenberg SM, Rebeck GW.

J Biol Chem. 2001 Aug 31;276(35):32860-6. Epub 2001 Jul 5.

PubMed [citation]
PMID:
11441013
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587274.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect APP protein function (PMID: 19061884, 11441013, 10821838, 8610157). This variant has been observed in individual(s) with hereditary cerebral amyloid angiopathy and in individual(s) with Alzheimer's disease (PMID: 2111584, 23919771, 11004129). This variant has also been shown to segregate with disease. This variant is also known as p.Glu22Gln in the literature. ClinVar contains an entry for this variant (Variation ID: 18087). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 693 of the APP protein (p.Glu693Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.

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

Last Updated: Sep 29, 2024