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NM_001377265.1(MAPT):c.2126A>T (p.Lys709Met) AND Frontotemporal dementia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 10, 2005
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000015338.27

Allele description [Variation Report for NM_001377265.1(MAPT):c.2126A>T (p.Lys709Met)]

NM_001377265.1(MAPT):c.2126A>T (p.Lys709Met)

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.2126A>T (p.Lys709Met)
HGVS:
  • NC_000017.11:g.46014277A>T
  • NG_007398.2:g.124815A>T
  • NM_001123066.4:c.1955A>T
  • NM_001123067.4:c.863A>T
  • NM_001203251.2:c.770A>T
  • NM_001203252.2:c.857A>T
  • NM_001377265.1:c.2126A>TMANE SELECT
  • NM_001377266.1:c.1835A>T
  • NM_001377267.1:c.770A>T
  • NM_001377268.1:c.683A>T
  • NM_005910.6:c.950A>T
  • NM_016834.5:c.776A>T
  • NM_016835.5:c.1901A>T
  • NM_016841.5:c.683A>T
  • NP_001116538.2:p.Lys652Met
  • NP_001116539.1:p.Lys288Met
  • NP_001190180.1:p.Lys257Met
  • NP_001190181.1:p.Lys286Met
  • NP_001364194.1:p.Lys709Met
  • NP_001364195.1:p.Lys612Met
  • NP_001364196.1:p.Lys257Met
  • NP_001364197.1:p.Lys228Met
  • NP_005901.2:p.Lys317Met
  • NP_058518.1:p.Lys259Met
  • NP_058519.3:p.Lys634Met
  • NP_058525.1:p.Lys228Met
  • LRG_660t1:c.1901A>T
  • LRG_660t2:c.2126A>T
  • LRG_660:g.124815A>T
  • LRG_660p1:p.Lys634Met
  • LRG_660p2:p.Lys709Met
  • NC_000017.10:g.44091643A>T
  • NG_007398.1:g.124857A>T
  • NR_165166.1:n.781A>T
  • P10636:p.Lys634Met
Protein change:
K228M; LYS317MET
Links:
UniProtKB: P10636#VAR_037440; OMIM: 157140.0024; dbSNP: rs63750092
NCBI 1000 Genomes Browser:
rs63750092
Molecular consequence:
  • NM_001123066.4:c.1955A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001123067.4:c.863A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001203251.2:c.770A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001203252.2:c.857A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377265.1:c.2126A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377266.1:c.1835A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377267.1:c.770A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377268.1:c.683A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005910.6:c.950A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016834.5:c.776A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016835.5:c.1901A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016841.5:c.683A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_165166.1:n.781A>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000035597OMIM
no assertion criteria provided
Pathogenic
(May 10, 2005) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.

Zarranz JJ, Ferrer I, Lezcano E, Forcadas MI, Eizaguirre B, Atarés B, Puig B, Gómez-Esteban JC, Fernández-Maiztegui C, Rouco I, Pérez-Concha T, Fernández M, Rodríguez O, Rodríguez-Martínez AB, de Pancorbo MM, Pastor P, Pérez-Tur J.

Neurology. 2005 May 10;64(9):1578-85.

PubMed [citation]
PMID:
15883319

Details of each submission

From OMIM, SCV000035597.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In affected members of 2 families from the Basque country in Spain with a tauopathy best described as frontotemporal dementia with parkinsonism (600274), Zarranz et al. (2005) identified a heterozygous A-to-T transversion in exon 11 of the MAPT gene, resulting in a lys317-to-met (K317M) substitution. Mean age at disease onset was 48 years, characterized by dysarthria and features of parkinsonism. All patients developed parkinsonism and a pyramidal syndrome, and half had amyotrophy. Other variable features included supranuclear gaze palsy, bulbar palsy, and dystonia. Although behavioral changes were not a prominent feature, most patients had frontal signs, and cognitive decline appeared late in the disease. All patients eventually became fully dependent, wheelchair- or bed-bound, tetraplegic, mute, and unable to feed orally. Neuropathologic examination showed frontal and temporal lobe atrophy, severe neuronal loss in the substantia nigra, and diffuse patchy neuronal loss and gliosis with numerous tau- and ubiquitin-positive neurons. Six of 7 spinal cords examined showed severe neuronal loss in the anterior horn and degeneration of the corticospinal tracts, similar to that seen in amyotrophic lateral sclerosis. Two bands of phospho-tau of 68 and 64 kD were observed in brain tissue from 1 patient. Zarranz et al. (2005) emphasized the motor component of the syndrome in these patients. Haplotype analysis suggested a common origin in the 2 families, and genealogic analysis identified a probable common ancestor born in 1782.

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

Last Updated: Sep 1, 2024