VCV000013731.16 - ClinVar

NM_000593.6(TAP1):c.1976G>A (p.Arg659Gln)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Likely benign (2)

3 out of 6 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000593.6(TAP1):c.1976G>A (p.Arg659Gln)

Variation ID: 13731 Accession: VCV000013731.16

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.32 6: 32847132 (GRCh38) [ NCBI UCSC ] 6: 32814909 (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	Sep 22, 2026	Feb 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000593.6:c.1976G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000584.3:p.Arg659Gln	missense
NM_001292022.2:c.1373G>A	NP_001278951.1:p.Arg458Gln	missense
NC_000006.12:g.32847132C>T
NC_000006.11:g.32814909C>T
NG_011759.1:g.11840G>A
NG_028165.1:g.2804G>A
LRG_1328:g.2804G>A
LRG_166:g.11840G>A
LRG_166t1:c.1976G>A	LRG_166p1:p.Arg659Gln
	Q03518:p.Arg719Gln

... more HGVS ... less HGVS

Protein change

R719Q, R458Q

Other names

R659Q

Canonical SPDI

NC_000006.12:32847131:C:T

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.

0.00080 (T)

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

1000 Genomes Project 30x 0.00062

1000 Genomes Project 0.00080

Trans-Omics for Precision Medicine (TOPMed) 0.00087

The Genome Aggregation Database (gnomAD) 0.00093

The Genome Aggregation Database (gnomAD) 0.00096

The Genome Aggregation Database (gnomAD), exomes 0.00120

The Genome Aggregation Database (gnomAD), exomes 0.00158

Exome Aggregation Consortium (ExAC) 0.00159

Links

ClinGen: CA123407 UniProtKB: Q03518#VAR_013173 OMIM: 170260.0003 dbSNP: rs121917702 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.
TAP1		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	484	537

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.
TAP1 deficiency, somatic	Pathogenic (1)	no assertion criteria provided	Jun 1, 1996	RCV000014734.5
MHC class I deficiency	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2026	RCV000554627.14
not provided	Uncertain significance (3)	criteria provided, single submitter	Oct 23, 2024	RCV001725932.2

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.	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.
Likely benign (Nov 02, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	MHC class I deficiency 1	Fulgent Genetics, Fulgent Genetics Accession: SCV002804753.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (Feb 01, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	MHC class I deficiency 1	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000642034.10 First in ClinVar: Dec 26, 2017 Last updated: Mar 07, 2026	Publications: PubMed (1) PubMed: 28492532 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Oct 23, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Blueprint Genetics Accession: SCV007979397.1 First in ClinVar: Sep 22, 2026 Last updated: Sep 22, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001963247.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Jun 01, 1996) N Not contributing to aggregate classification	no assertion criteria provided	TAP1 DEFICIENCY, SOMATIC	OMIM Accession: SCV000034989.2 First in ClinVar: Apr 04, 2013 Last updated: May 26, 2024	Publications: PubMed (1) PubMed: 8640228 Observation: 1 Collection method: literature only Allele origin: somatic Affected status: not provided more Observation 1 Collection method: literature only Allele origin: somatic Affected status: not provided Comment on evidence: In a human small cell lung cancer cell line, Chen et al. (1996) identified heterozygosity for an R659Q allele at the TAP1 locus. Only the … (more) In a human small cell lung cancer cell line, Chen et al. (1996) identified heterozygosity for an R659Q allele at the TAP1 locus. Only the R659Q allele was transcribed into RNA. Even though the protein was expressed, the cells acted as if they were TAP-deficient and were restored to normal by transfection of a functional TAP1 allele. Thus the cells had a defect in the conveying of intracellular peptides into the endoplasmic reticulum for complex formation with class I MHC and subsequent recognition by cytotoxic T lymphocytes. (less)

Uncertain significance (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV001973190.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer.	Chen HL	Nature genetics	1996	PMID: 8640228

Text-mined citations for rs121917702 ...

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 27, 2026