VCV000014246.3 - ClinVar

NM_001377265.1(MAPT):c.1991G>T (p.Gly664Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001377265.1(MAPT):c.1991G>T (p.Gly664Val)

Variation ID: 14246 Accession: VCV000014246.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 45996657 (GRCh38) [ NCBI UCSC ] 17: 44074023 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 20, 2014	May 10, 2021	May 6, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001377265.1:c.1991G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001364194.1:p.Gly664Val	missense
NM_001123066.4:c.1820G>T	NP_001116538.2:p.Gly607Val	missense
NM_001123067.4:c.728G>T	NP_001116539.1:p.Gly243Val	missense
NM_001203251.2:c.728G>T	NP_001190180.1:p.Gly243Val	missense
NM_001203252.2:c.815G>T	NP_001190181.1:p.Gly272Val	missense
NM_001377266.1:c.1793G>T	NP_001364195.1:p.Gly598Val	missense
NM_001377267.1:c.728G>T	NP_001364196.1:p.Gly243Val	missense
NM_001377268.1:c.641G>T	NP_001364197.1:p.Gly214Val	missense
NM_005910.6:c.815G>T	NP_005901.2:p.Gly272Val	missense
NM_016834.5:c.641G>T	NP_058518.1:p.Gly214Val	missense
NM_016835.5:c.1766G>T	NP_058519.3:p.Gly589Val	missense
NM_016841.5:c.641G>T	NP_058525.1:p.Gly214Val	missense
NR_165166.1:n.739G>T		non-coding transcript variant
NC_000017.11:g.45996657G>T
NC_000017.10:g.44074023G>T
NG_007398.2:g.107195G>T
LRG_660:g.107195G>T
LRG_660t1:c.1766G>T	LRG_660p1:p.Gly589Val
LRG_660t2:c.1991G>T	LRG_660p2:p.Gly664Val
	P10636:p.Gly589Val

... more HGVS ... less HGVS

Protein change

G272V, G589V, G243V, G607V, G214V, G598V, G664V

Other names

Canonical SPDI

NC_000017.11:45996656:G:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA225421 UniProtKB: P10636#VAR_010345 OMIM: 157140.0002 dbSNP: rs63750376 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MAPT		No evidence available	No evidence available	GRCh38 GRCh38 GRCh38 GRCh37	506	640

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Frontotemporal dementia	Pathogenic (1)	no assertion criteria provided	May 6, 2021	RCV000015315.30
not provided	not provided (1)	no classification provided	-	RCV000084519.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 06, 2021)	no assertion criteria provided Method: literature only	DEMENTIA, FRONTOTEMPORAL, WITH PARKINSONISM Affected status: not provided Allele origin: germline	OMIM Accession: SCV000035574.4 First in ClinVar: Apr 04, 2013 Last updated: May 10, 2021	Publications: PubMed (3) PubMed: 10767321‚ 11402146‚ 8673924 Comment on evidence: In a second large Dutch kindred with frontotemporal dementia (600274) reported by Heutink et al. (1997) as an example of hereditary Pick disease, Hutton et … (more) In a second large Dutch kindred with frontotemporal dementia (600274) reported by Heutink et al. (1997) as an example of hereditary Pick disease, Hutton et al. (1998) found a gly272-to-val mutation (G272V) that affected a highly conserved residue within the microtubule-associated domain, encoded by exon 9 of the MAPT gene. Using purified recombinant proteins, Alonso et al. (2004) showed that several FTDP17-associated tau mutations, including G272V, made tau a more favorable substrate for abnormal hyperphosphorylation compared with wildtype tau. Both the phosphorylation kinetics, due to induced conformational changes, and the phosphorylation stoichiometry, due to increased phosphorylation of more than a single site, were more favorable in the mutant proteins. The mutant proteins polymerized into filaments more readily than wildtype tau, leading to decreased ability to bind wildtype tau. (less)
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	VIB Department of Molecular Genetics, University of Antwerp Accession: SCV000116655.1 First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014 Comment: http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg18&id=ADM_177

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Missense and splice site mutations in tau associated with FTDP-17: multiple pathogenic mechanisms.	Hutton M	Neurology	2001	PMID: 11402146
Untangling tau-related dementia.	Heutink P	Human molecular genetics	2000	PMID: 10767321
Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules.	Alonso AC	Nature medicine	1996	PMID: 8673924

Text-mined citations for rs63750376 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001377265.1(MAPT):c.1991G>T (p.Gly664Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs63750376 ...