VCV000013730.21 - ClinVar

NM_000593.6(TAP1):c.1910A>G (p.Asp637Gly)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (4); Likely benign (3)

7 out of 21 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

Functional data are available for this variant

Variant Details

Identifiers

NM_000593.6(TAP1):c.1910A>G (p.Asp637Gly)

Variation ID: 13730 Accession: VCV000013730.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.32 6: 32847198 (GRCh38) [ NCBI UCSC ] 6: 32814975 (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 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000593.6:c.1910A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000584.3:p.Asp637Gly	missense
NM_001292022.2:c.1307A>G	NP_001278951.1:p.Asp436Gly	missense
NC_000006.12:g.32847198T>C
NC_000006.11:g.32814975T>C
NG_011759.1:g.11774A>G
NG_028165.1:g.2738A>G
LRG_1328:g.2738A>G
LRG_166:g.11774A>G
LRG_166t1:c.1910A>G	LRG_166p1:p.Asp637Gly
	Q03518:p.Asp697Gly

... more HGVS ... less HGVS

Protein change

D697G, D436G

Other names

D637G

Canonical SPDI

NC_000006.12:32847197:T:C

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.

0.19149 (C)

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

The Genome Aggregation Database (gnomAD), exomes 0.14632

The Genome Aggregation Database (gnomAD), exomes 0.17024

Exome Aggregation Consortium (ExAC) 0.17393

The Genome Aggregation Database (gnomAD) 0.17500

The Genome Aggregation Database (gnomAD) 0.17502

Trans-Omics for Precision Medicine (TOPMed) 0.17540

1000 Genomes Project 0.19149

1000 Genomes Project 30x 0.19316

Links

ClinGen: CA123405 UniProtKB: Q03518#VAR_000093 OMIM: 170260.0002 dbSNP: rs1135216 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.
PEPTIDE TRANSPORTER PSF1 POLYMORPHISM	Benign (1)	no assertion criteria provided	May 1, 1992	RCV000014733.3
not specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 21, 2026	RCV000454796.7
MHC class I deficiency	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV001518268.12

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 (Jan 21, 2026) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV007344888.1 First in ClinVar: Feb 07, 2026 Last updated: Feb 07, 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

Benign (Mar 28, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000540483.1 First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017	Comment: show Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Method: Genome/Exome Filtration

Benign (Jul 15, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	MHC class I deficiency 1	Genome-Nilou Lab Accession: SCV002062197.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely benign (Jan 18, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	MHC class I deficiency 1	Fulgent Genetics, Fulgent Genetics Accession: SCV002812956.1 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

Benign (Jun 28, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007301642.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 36

Benign (Feb 04, 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: SCV001726931.6 First in ClinVar: Jun 15, 2021 Last updated: Feb 23, 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

Likely benign (Nov 26, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Blueprint Genetics Accession: SCV007979400.1 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

Benign (May 01, 1992) N Not contributing to aggregate classification	no assertion criteria provided	PEPTIDE TRANSPORTER PSF1 POLYMORPHISM	OMIM Accession: SCV000034988.2 First in ClinVar: Apr 04, 2013 Last updated: May 26, 2024	Publications: PubMed (1) PubMed: 1570316 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: By SSCP analysis followed by DNA sequencing, Colonna et al. (1992) identified an A-to-G transition at nucleotide 1982 in segment 8 of the PSF1 gene, … (more) By SSCP analysis followed by DNA sequencing, Colonna et al. (1992) identified an A-to-G transition at nucleotide 1982 in segment 8 of the PSF1 gene, replacing asp637 with glycine. The allele designated PSF1A showed linkage of ile333 and asp637; val333 together with gly637 or asp637 form the PSF1B and PSF1C alleles, respectively. (less)

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Allelic variants of the human putative peptide transporter involved in antigen processing.	Colonna M	Proceedings of the National Academy of Sciences of the United States of America	1992	PMID: 1570316

Submissions - Functional Data

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0032)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814975 from -18.20 to 0.44 bits. Significant p-values: junction spanning - intron inclusion (22 reads, p=0.0032). ; Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (22 reads, p=0.0032). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659393.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-A8-A08A), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Familial cancer of breast
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-A8-A08A
Tissue: Breast Invasive Carcinoma (BRCA)
Collection method: in vitro
Species: human
Number of controls: 106

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0255)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (158 reads, p=0.0255). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659394.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GS-A9U3), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-GS-A9U3
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0069)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (208 reads, p=0.0069). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659396.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FF-A7CQ), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-FF-A7CQ
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0039),read abundance - intron inclusion (p=0.0062)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (230 reads, p=0.0039), read abundance - intron inclusion (4542 reads, p=0.0062). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659397.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FA-A6HN), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-FA-A6HN
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

read abundance - intron inclusion (p=0.0082)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: read abundance - intron inclusion (4348 reads, p=0.0082). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659398.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FF-A7CX), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-FF-A7CX
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0165)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (175 reads, p=0.0165). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659400.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FA-A4XK), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-FA-A4XK
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0012)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (179 reads, p=0.0012). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659401.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-XU-A92Q), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Thymoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-XU-A92Q
Tissue: Thymoma (THYM)
Collection method: in vitro
Species: human
Number of controls: 100

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0128)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (81 reads, p=0.0128). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659404.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-ND-A4WC), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Uterine carcinosarcoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-ND-A4WC
Tissue: Uterine Carcinosarcoma (UCS)
Collection method: in vitro
Species: human
Number of controls: 139

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0224)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (72 reads, p=0.0224). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659405.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-NA-A4R0), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Uterine carcinosarcoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-NA-A4R0
Tissue: Uterine Carcinosarcoma (UCS)
Collection method: in vitro
Species: human
Number of controls: 139

functionally abnormal -- retained intron

assessed by RNAseq

Result:

read abundance - intron inclusion (p=0.0038)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: read abundance - intron inclusion (4885 reads, p=0.0038). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659399.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FF-8042), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-FF-8042
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 137

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0152)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (135 reads, p=0.0152). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659402.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-3X-AAVE), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Cholangiocarcinoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-3X-AAVE
Tissue: Cholangiocarcinoma (CHOL)
Collection method: in vitro
Species: human
Number of controls: 34

functionally abnormal -- retained intron

assessed by RNAseq

Result:

read abundance - intron inclusion (p=0.0093)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: read abundance - intron inclusion (1453 reads, p=0.0093). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659403.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-N5-A59F), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Uterine carcinosarcoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-N5-A59F
Tissue: Uterine Carcinosarcoma (UCS)
Collection method: in vitro
Species: human
Number of controls: 139

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0198)

Modifies an exonic cryptic donor site at NC_000006.11:g.32814979 from 3.31 to 6.49 bits. Significant p-values: junction spanning - intron inclusion (74 reads, p=0.0198). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006659407.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-N5-A4RT), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Uterine carcinosarcoma
Transcript, protein change: NM_000593.6:c.1910A>G, D637G
Molecular phenotype measured: splicing
Cell line: TCGA-N5-A4RT
Tissue: Uterine Carcinosarcoma (UCS)
Collection method: in vitro
Species: human
Number of controls: 139

Text-mined citations for rs1135216 ...

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 22, 2026