NM_000021.4(PSEN1):c.338+1del AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 11, 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:: RCV000084293.3

Allele description [Variation Report for NM_000021.4(PSEN1):c.338+1del]

NM_000021.4(PSEN1):c.338+1del

Gene:

PSEN1:presenilin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q24.2

Genomic location:

Preferred name:

NM_000021.4(PSEN1):c.338+1del

HGVS:

NC_000014.9:g.73171048del
NG_007386.2:g.39578del
NG_129431.1:g.623del
NM_000021.4:c.338+1delMANE SELECT
NM_007318.3:c.326+1del
LRG_224t1:c.338+1del
LRG_224:g.39578del
NC_000014.8:g.73637756del
NC_000014.8:g.73637756delG
NM_000021.3:c.338+1del

Links:

OMIM: 104311.0018; dbSNP: rs63751475

NCBI 1000 Genomes Browser:

rs63751475

Molecular consequence:

NM_000021.4:c.338+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007318.3:c.326+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000116429	VIB Department of Molecular Genetics, University of Antwerp	no classification provided	not provided	not provided	not provided
SCV002770639	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Aug 11, 2021)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 10401002, 12552037, 11524469, 27777022, 24880964, 26481686, 32395715, 10775535, 34319632, 30590039, 9443865, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000116429

VIB Department of Molecular Genetics, University of Antwerp

no classification provided

not provided

SCV002770639

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Aug 11, 2021)

unknown

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg18&id=ADM_6: SCV000116429

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aberrant splicing in the presenilin-1 intron 4 mutation causes presenile Alzheimer's disease by increased Abeta42 secretion.

De Jonghe C, Cruts M, Rogaeva EA, Tysoe C, Singleton A, Vanderstichele H, Meschino W, Dermaut B, Vanderhoeven I, Backhovens H, Vanmechelen E, Morris CM, Hardy J, Rubinsztein DC, St George-Hyslop PH, Van Broeckhoven C.

Hum Mol Genet. 1999 Aug;8(8):1529-40.

PubMed [citation]

PMID:: 10401002

Early onset familial Alzheimer's disease: Mutation frequency in 31 families.

Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, Houlden H, Rossor MN, Collinge J.

Neurology. 2003 Jan 28;60(2):235-9.

PubMed [citation]

PMID:: 12552037

See all PubMed Citations (12)

Details of each submission

From VIB Department of Molecular Genetics, University of Antwerp, SCV000116429.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV002770639.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal RNA splicing, and subsequent abnormal protein function. Studies show the altered protein results in increased amyloid-beta-42 secretion, and overall reduced gamma-secretase activity (PMID: 10401002, 26481686, 32395715). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. This variant appears to be associated with disease in at least one family.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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