VCV000000409.5 - ClinVar

NC_000004.11:g.3076606GCA[40_?]

Germline

Practice guidelines

Practice guidelines. Learn more about how ClinVar calculates review status.

Pathogenic

for Huntington disease

Classification is based on the practice guideline submission

Jul 2014 by American College of Medical Genetics and Genomics (ACMG)

The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000004.11:g.3076606GCA[40_?]

Variation ID: 409 Accession: VCV000000409.5

Type and length

Microsatellite, -

Location

Cytogenetic: 4p16.3 4: 3074935-3074936 (GRCh38) [ NCBI UCSC ] 4: 3076604-3076660 (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	Apr 4, 2013	Nov 13, 2022	Jul 31, 2014

HGVS

Nucleotide	Protein	Molecular consequence
NM_002111.6:c.53AGC[(41_?)]
NM_002111.8:c.52CAG[40_?]
NM_002111.8:c.52CAR[(40_?)]
NG_009378.1:g.5198AGC[(41_?)]
NG_009378.1:g.5198AGC[40_?]
NG_009378.1:g.5198_5200(41_?)
LRG_763:g.5198_5200(41_?)
LRG_763t1:c.52CAG[40_?]
	LRG_763p1:p.Gln40(41_?)
	NP_002102.4:p.Gln40(41_?)

... more HGVS ... less HGVS

Protein change

Other names

NC_000004.11:g.3076606GCA[(40_?)]

Canonical SPDI

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

OMIM: 613004.0001 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.
HTT		-	-	GRCh38 GRCh37	742	916
LOC109461479	-	-	-	GRCh38	-	91
LOC129929027	-	-	-	GRCh38	-	95

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.
Huntington disease	Pathogenic (3)	practice guideline	Jul 31, 2014	RCV000030659.8

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.	Expand all rows Collapse all rows 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 (Jul 31, 2014) C Contributing to aggregate classification	practice guideline (Technical standards and guidelines for Huntington disease)	Huntington disease (Autosomal dominant inheritance)	American College of Medical Genetics and Genomics (ACMG) Accession: SCV001161434.1 First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020	Publications: PubMed (1) PubMed: 25356969 Bookshelf: NBK1305 Bookshelf: NBK1305 Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Pathogenic (May 15, 2010) N Not contributing to aggregate classification	no assertion criteria provided	HUNTINGTON DISEASE	OMIM Accession: SCV000020586.4 First in ClinVar: Apr 04, 2013 Last updated: Jan 10, 2020	Publications: PubMed (3) PubMed: 8401587‚ 20154343‚ 8755937 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: Huntington disease (HD; 143100) is caused by expansion of a polymorphic trinucleotide repeat (CAG)n, encoding glutamine, located in the N-terminal coding region of the HTT … (more) Huntington disease (HD; 143100) is caused by expansion of a polymorphic trinucleotide repeat (CAG)n, encoding glutamine, located in the N-terminal coding region of the HTT gene. In normal individuals, the range of repeat numbers is 9 to 36. In those with HD, the repeat number is above 37 (Duyao et al., 1993). The trinucleotide repeat expansion was identified in affected members of 75 families with HD by the Huntington's Disease Collaborative Research Group (1993). The families came from a variety of ethnic backgrounds and demonstrated a variety of 4p16.3 haplotypes. Gellera et al. (1996) noted that the unstable (CAG)n repeat lies immediately upstream from a moderately polymorphic polyproline-encoding (CCG)n repeat. They noted further that a number of reports in the literature indicated that in normal subjects the number of (CAG)n repeats ranges from 9 to 36, while in HD patients it ranges from 37 to 100. The downstream (CCG)n repeat may vary in size between 7 and 12 repeats in both affected and normal individuals. They reported the occurrence of a CAA trinucleotide deletion (nucleotides 433-435) in HD chromosomes in 2 families that, because of its position within the conventional antisense primer hd447, hampered HD mutation detection if only the (CAG)n tract were amplified. Therefore, Gellera et al. (1996) stressed the importance of using a series of 3 diagnostic PCR reactions: one that amplified the (CAG)n tract alone, one that amplified the (CCG)n tract alone, and one that amplified the whole region. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	Huntington disease	GeneReviews Accession: SCV000054534.2 First in ClinVar: Apr 04, 2013 Last updated: Nov 13, 2022	Publications: Bookshelf: NBK1305 Bookshelf: NBK1305 Comment: show Repeat Range: Full penetrance (less) Observation: 1 Collection method: literature only Allele origin: germline Affected status: unknown Observation 1 Collection method: literature only Allele origin: germline Affected status: unknown

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Huntington Disease.	Adam MP	-	2020	PMID: 20301482
An ovine transgenic Huntington's disease model.	Jacobsen JC	Human molecular genetics	2010	PMID: 20154343
Errors in Huntington disease diagnostic test caused by trinucleotide deletion in the IT15 gene.	Gellera C	American journal of human genetics	1996	PMID: 8755937
Trinucleotide repeat length instability and age of onset in Huntington's disease.	Duyao M	Nature genetics	1993	PMID: 8401587

Text-mined citations for this variant ...

Record last updated Mar 23, 2024

ClinVar Genomic variation as it relates to human health

NC_000004.11:g.3076606GCA[40_?]

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for this variant ...