NM_001377265.1(MAPT):c.47G>T (p.Gly16Val) AND Frontotemporal dementia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 11, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000662117.12

Allele description [Variation Report for NM_001377265.1(MAPT):c.47G>T (p.Gly16Val)]

NM_001377265.1(MAPT):c.47G>T (p.Gly16Val)

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.47G>T (p.Gly16Val)

HGVS:

NC_000017.11:g.45962384G>T
NG_007398.2:g.72922G>T
NM_001123066.4:c.47G>T
NM_001123067.4:c.47G>T
NM_001203251.2:c.47G>T
NM_001203252.2:c.47G>T
NM_001377265.1:c.47G>TMANE SELECT
NM_001377266.1:c.47G>T
NM_001377267.1:c.47G>T
NM_001377268.1:c.47G>T
NM_005910.6:c.47G>T
NM_016834.5:c.47G>T
NM_016835.5:c.47G>T
NM_016841.5:c.47G>T
NP_001116538.2:p.Gly16Val
NP_001116539.1:p.Gly16Val
NP_001190180.1:p.Gly16Val
NP_001190181.1:p.Gly16Val
NP_001364194.1:p.Gly16Val
NP_001364195.1:p.Gly16Val
NP_001364196.1:p.Gly16Val
NP_001364197.1:p.Gly16Val
NP_005901.2:p.Gly16Val
NP_005901.2:p.Gly16Val
NP_058518.1:p.Gly16Val
NP_058519.3:p.Gly16Val
NP_058525.1:p.Gly16Val
LRG_660t1:c.47G>T
LRG_660t2:c.47G>T
LRG_660:g.72922G>T
LRG_660p1:p.Gly16Val
LRG_660p2:p.Gly16Val
NC_000017.10:g.44039750G>T
NG_007398.1:g.72963G>T
NM_005910.5:c.47G>T
NM_016841.4:c.47G>T
NR_165166.1:n.197G>T

Protein change:

G16V

Links:

dbSNP: rs755131800

NCBI 1000 Genomes Browser:

rs755131800

Molecular consequence:

NM_001123066.4:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001123067.4:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001203251.2:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001203252.2:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377265.1:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377266.1:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377267.1:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377268.1:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005910.6:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016834.5:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016835.5:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016841.5:c.47G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_165166.1:n.197G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV000784460	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 5, 2018)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001229674	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 11, 2019)	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

SCV000784460

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 5, 2018)

inherited

clinical testing

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

SCV001229674

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 11, 2019)

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
not provided	inherited	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

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 Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000784460.2

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

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

From Invitae, SCV001229674.5

#	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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MAPT-related conditions. ClinVar contains an entry for this variant (Variation ID: 548576). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glycine with valine at codon 16 of the MAPT protein (p.Gly16Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine.

#	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: Sep 1, 2024

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