NM_001377265.1(MAPT):c.25G>A (p.Glu9Lys) AND Frontotemporal dementia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 14, 2022
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:: RCV001869641.8

Allele description [Variation Report for NM_001377265.1(MAPT):c.25G>A (p.Glu9Lys)]

NM_001377265.1(MAPT):c.25G>A (p.Glu9Lys)

Gene:

MAPT:microtubule associated protein tau [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_001377265.1(MAPT):c.25G>A (p.Glu9Lys)

HGVS:

NC_000017.11:g.45962362G>A
NG_007398.2:g.72900G>A
NM_001123066.4:c.25G>A
NM_001123067.4:c.25G>A
NM_001203251.2:c.25G>A
NM_001203252.2:c.25G>A
NM_001377265.1:c.25G>AMANE SELECT
NM_001377266.1:c.25G>A
NM_001377267.1:c.25G>A
NM_001377268.1:c.25G>A
NM_005910.6:c.25G>A
NM_016834.5:c.25G>A
NM_016835.5:c.25G>A
NM_016841.5:c.25G>A
NP_001116538.2:p.Glu9Lys
NP_001116539.1:p.Glu9Lys
NP_001190180.1:p.Glu9Lys
NP_001190181.1:p.Glu9Lys
NP_001364194.1:p.Glu9Lys
NP_001364195.1:p.Glu9Lys
NP_001364196.1:p.Glu9Lys
NP_001364197.1:p.Glu9Lys
NP_005901.2:p.Glu9Lys
NP_058518.1:p.Glu9Lys
NP_058519.3:p.Glu9Lys
NP_058525.1:p.Glu9Lys
LRG_660t1:c.25G>A
LRG_660t2:c.25G>A
LRG_660:g.72900G>A
LRG_660p1:p.Glu9Lys
LRG_660p2:p.Glu9Lys
NC_000017.10:g.44039728G>A
NG_007398.1:g.72941G>A
NR_165166.1:n.175G>A

Protein change:

E9K

Links:

dbSNP: rs762595428

NCBI 1000 Genomes Browser:

rs762595428

Molecular consequence:

NM_001123066.4:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001123067.4:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001203251.2:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001203252.2:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377265.1:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377266.1:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377267.1:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377268.1:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005910.6:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016834.5:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016835.5:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016841.5:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_165166.1:n.175G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002124370	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 14, 2022)	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

SCV002124370

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 14, 2022)

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, SCV002124370.3

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1335279). This variant has not been reported in the literature in individuals affected with MAPT-related conditions. This variant is present in population databases (rs762595428, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 9 of the MAPT protein (p.Glu9Lys).

#	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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