NM_000484.4(APP):c.2155A>C (p.Thr719Pro) AND Alzheimer disease type 1

Clinical significance:Likely pathogenic (Last evaluated: Oct 27, 2021)
Review status:1 star out of maximum of 4 stars
criteria provided, single submitter

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Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV001842233.1

Allele description [Variation Report for NM_000484.4(APP):c.2155A>C (p.Thr719Pro)]

NM_000484.4(APP):c.2155A>C (p.Thr719Pro)

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.2155A>C (p.Thr719Pro)

Other names:

p.Thr719Pro

HGVS:

NC_000021.9:g.25891778T>G
NG_007376.2:g.284351A>C
NM_000484.4:c.2155A>CMANE SELECT
NM_001136016.3:c.2083A>C
NM_001136129.3:c.1762A>C
NM_001136130.3:c.1987A>C
NM_001136131.3:c.1825A>C
NM_001204301.2:c.2101A>C
NM_001204302.2:c.2044A>C
NM_001204303.2:c.1876A>C
NM_001385253.1:c.1987A>C
NM_201413.3:c.2098A>C
NM_201414.3:c.1930A>C
NP_000475.1:p.Thr719Pro
NP_001129488.1:p.Thr695Pro
NP_001129601.1:p.Thr588Pro
NP_001129602.1:p.Thr663Pro
NP_001129603.1:p.Thr609Pro
NP_001191230.1:p.Thr701Pro
NP_001191231.1:p.Thr682Pro
NP_001191232.1:p.Thr626Pro
NP_001372182.1:p.Thr663Pro
NP_958816.1:p.Thr700Pro
NP_958817.1:p.Thr644Pro
NC_000021.8:g.27264090T>G

Protein change:

T588P

Molecular consequence:

NM_000484.4:c.2155A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136016.3:c.2083A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136129.3:c.1762A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136130.3:c.1987A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136131.3:c.1825A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001204301.2:c.2101A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001204302.2:c.2044A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001204303.2:c.1876A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385253.1:c.1987A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201413.3:c.2098A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201414.3:c.1930A>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

Observations:

Condition(s)

Name:: Alzheimer disease type 1
Synonyms:: Early-onset familial form of Alzheimer disease; ALZHEIMER DISEASE, FAMILIAL, 1; ALZHEIMER DISEASE, FAMILIAL, 1, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0007088; MedGen: C1863052; OMIM: 104300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002102396	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter ACMG Guidelines, 2015	Likely pathogenic (Oct 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002102396

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

ACMG Guidelines, 2015

Likely pathogenic
(Oct 27, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

Help

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Hindu	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV002102396.1

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

Description

A heterozygous missense variation in exon 17 of the APP gene that results in the amino acid substitution of Proline for Threonine at codon 719 was detected. The observed variant c.2155A>C (p.Thr719Pro) has not been reported in the 1000 genomes and gnomAD database. The in-silico prediction of the variant are probably damaging by PolyPhen-2 and damaging by SIFT, MutationTaster2 and LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a likely pathogenic variant.

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

Last Updated: Nov 19, 2022

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