NM_000021.4(PSEN1):c.1073G>C (p.Arg358Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 18, 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:: RCV001314550.8

Allele description [Variation Report for NM_000021.4(PSEN1):c.1073G>C (p.Arg358Pro)]

NM_000021.4(PSEN1):c.1073G>C (p.Arg358Pro)

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.1073G>C (p.Arg358Pro)

HGVS:

NC_000014.9:g.73211886G>C
NG_007386.2:g.80416G>C
NM_000021.4:c.1073G>CMANE SELECT
NM_007318.3:c.1061G>C
NP_000012.1:p.Arg358Pro
NP_015557.2:p.Arg354Pro
LRG_224t1:c.1073G>C
LRG_224:g.80416G>C
LRG_224p1:p.Arg358Pro
NC_000014.8:g.73678594G>C
NM_000021.3:c.1073G>C

Protein change:

R354P

Links:

dbSNP: rs63751174

NCBI 1000 Genomes Browser:

rs63751174

Molecular consequence:

NM_000021.4:c.1073G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007318.3:c.1061G>C - 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 (FTD1)
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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001505086	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 18, 2020)	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

SCV001505086

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 18, 2020)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001505086.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PSEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 448142). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 358 of the PSEN1 protein (p.Arg358Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline.

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

Last Updated: Oct 20, 2024

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