VCV000009982.26 - ClinVar

NM_002294.3(LAMP2):c.928G>A (p.Val310Ile)

Germline

Classification

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

Pathogenic
Pathogenic (5)

5 out of 14 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_002294.3(LAMP2):c.928G>A (p.Val310Ile)

Variation ID: 9982 Accession: VCV000009982.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120442599 (GRCh38) [ NCBI UCSC ] X: 119576454 (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 24, 2015	Feb 15, 2026	Mar 18, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.928G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Val310Ile	missense
NM_001122606.1:c.928G>A	NP_001116078.1:p.Val310Ile	missense
NM_013995.2:c.928G>A	NP_054701.1:p.Val310Ile	missense
NC_000023.11:g.120442599C>T
NC_000023.10:g.119576454C>T
NG_007995.1:g.31751G>A
LRG_749:g.31751G>A
LRG_749t1:c.928G>A	LRG_749p1:p.Val310Ile
LRG_749t2:c.928G>A	LRG_749p2:p.Val310Ile
LRG_749t3:c.928G>A	LRG_749p3:p.Val310Ile

... more HGVS ... less HGVS

Protein change

V310I

Other names

p.V310I:GTT>ATT

Canonical SPDI

NC_000023.11:120442598: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.

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

Links

ClinGen: CA120868 OMIM: 309060.0010 dbSNP: rs104894858 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.
LAMP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	955	1135

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.
Danon disease	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Mar 18, 2025	RCV000010663.22
not provided	Pathogenic (4)	criteria provided, single submitter	Sep 10, 2020	RCV000157981.6
Danon disease Hypertrophic cardiomyopathy	Pathogenic (1)	criteria provided, single submitter	Feb 20, 2014	RCV000844638.4
Cardiovascular phenotype	Pathogenic (1)	criteria provided, single submitter	Mar 19, 2021	RCV002371769.2

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.
Pathogenic (Feb 20, 2014) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	Hypertrophic cardiomyopathy Danon disease (X-linked inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000061093.5 First in ClinVar: May 03, 2013 Last updated: Aug 31, 2019	Publications: PubMed (5) PubMed: 15673802‚ 16217705‚ 18555174‚ 19318653‚ 19373884 Comment: show The p.Val310Ile variant in LAMP2 has been reported in multiple individuals with HCM or Danon disease, where it showed segregation with disease in multiple famil ies and de novo occurrence in at least 1 family (Arad 2005, Bertini 2005, Burusn ukul, 2008, Maron 2009, Sabourdy 2009, LMM data). It has not been identified in large population studies. It was shown to alter splicing of the LAMP2 mRNA, resu lting in a frameshift and subsequent premature termination in exon 8 (Arad 2005, Sabourdy 2009). This variant has been identified in ClinVar (Variant ID: 9982). Loss of function of the LAMP2 gene is an established disease mechanism and is t ypically associated with Danon disease. In summary, this variant meets criteria to be classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 7

Pathogenic (Mar 19, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002686542.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (7) PubMed: 15673802‚ 16217705‚ 18555174‚ 19373884‚ 25611685‚ 27532257‚ 29753918 Comment: show The c.928G>A pathogenic mutation (also known as p.V310I), located in coding exon 7 of the LAMP2 gene, results from a G to A substitution at nucleotide position 928. The amino acid change results in valine to isoleucine at codon 310, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This alteration has been reported de novo in a subject with hypertrophic cardiomyopathy (HCM) and Danon disease (Arad M et al. N Engl J Med, 2005 Jan;352:362-72). In addition, this mutation has been reported in HCM cohorts, subjects with Danon disease as well as other subjects with features of LAMP2-related disease (Sabourdy F et al. Muscle Nerve, 2009 Jun;39:837-44; Alfares AA et al. Genet Med, 2015 Nov;17:880-8; Walsh R et al. Genet Med, 2017 02;19:192-203; Gourzi P et al. Eur J Med Genet, 2019 Jan;62:77-80). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. In addition, as a missense substitution this is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Dec 11, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Classification criteria August 2017)	Danon disease (X-linked inheritance)	Institute of Human Genetics Munich, TUM University Hospital Accession: SCV001149822.2 First in ClinVar: Feb 03, 2020 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Zygosity: 1 Single Heterozygote Sex: female Tissue: blood

Pathogenic (Mar 18, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001401143.7 First in ClinVar: Jul 16, 2020 Last updated: Feb 15, 2026	Publications: PubMed (6) PubMed: 15673802‚ 16217705‚ 17576681‚ 19373884‚ 29753918‚ 9536098 Comment: show This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 310 of the LAMP2 protein (p.Val310Ile). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Danon disease or dilated cardiomyopathy (PMID: 15673802, 16217705, 19373884, 29753918). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 9982). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 7, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 16217705, 19373884). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Sep 10, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000207916.11 First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015	Comment: show Destroys a canonical splice donor site and results in the skipping of exon 7 (Arad et al., 2005); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18555174, 25611685, 29753918, 16217705, 15673802, 22695892, 19373884, 19318653, 20173215, 12398843, 27600940, 27532257, 33763395) (less) 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 (Jan 27, 2005) N Not contributing to aggregate classification	no assertion criteria provided	DANON DISEASE	OMIM Accession: SCV000030889.4 First in ClinVar: Apr 04, 2013 Last updated: Jun 03, 2022	Publications: PubMed (1) PubMed: 15673802 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: In a male proband with Danon disease (300257), described as glycogen storage disease presenting as hypertrophic cardiomyopathy, Arad et al. (2005) found a 928G-A transition … (more) In a male proband with Danon disease (300257), described as glycogen storage disease presenting as hypertrophic cardiomyopathy, Arad et al. (2005) found a 928G-A transition in the LAMP2 gene that resulted in a val310-to-ile (V310I) amino acid substitution. The mutation affected RNA processing and hence produced a frameshift (K289FS). Genetic studies demonstrated mosaicism: both mutant and wildtype LAMP2 sequences were identified despite a normal XY karyotype. (less)

Pathogenic (-) 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: SCV001742174.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 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 (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV001932866.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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 (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Study: VKGL Data-share Consensus Accession: SCV001952843.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 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

Comment:

The p.Val310Ile variant in LAMP2 has been reported in multiple individuals with HCM or Danon disease, where it showed segregation with disease in multiple famil ies and de novo occurrence in at least 1 family (Arad 2005, Bertini 2005, Burusn ukul, 2008, Maron 2009, Sabourdy 2009, LMM data). It has not been identified in large population studies. It was shown to alter splicing of the LAMP2 mRNA, resu lting in a frameshift and subsequent premature termination in exon 8 (Arad 2005, Sabourdy 2009). This variant has been identified in ClinVar (Variant ID: 9982). Loss of function of the LAMP2 gene is an established disease mechanism and is t ypically associated with Danon disease. In summary, this variant meets criteria to be classified as pathogenic.

Comment:

The c.928G>A pathogenic mutation (also known as p.V310I), located in coding exon 7 of the LAMP2 gene, results from a G to A substitution at nucleotide position 928. The amino acid change results in valine to isoleucine at codon 310, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This alteration has been reported de novo in a subject with hypertrophic cardiomyopathy (HCM) and Danon disease (Arad M et al. N Engl J Med, 2005 Jan;352:362-72). In addition, this mutation has been reported in HCM cohorts, subjects with Danon disease as well as other subjects with features of LAMP2-related disease (Sabourdy F et al. Muscle Nerve, 2009 Jun;39:837-44; Alfares AA et al. Genet Med, 2015 Nov;17:880-8; Walsh R et al. Genet Med, 2017 02;19:192-203; Gourzi P et al. Eur J Med Genet, 2019 Jan;62:77-80). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. In addition, as a missense substitution this is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

Comment:

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 310 of the LAMP2 protein (p.Val310Ile). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Danon disease or dilated cardiomyopathy (PMID: 15673802, 16217705, 19373884, 29753918). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 9982). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 7, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 16217705, 19373884). For these reasons, this variant has been classified as Pathogenic.

Comment:

Destroys a canonical splice donor site and results in the skipping of exon 7 (Arad et al., 2005); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18555174, 25611685, 29753918, 16217705, 15673802, 22695892, 19373884, 19318653, 20173215, 12398843, 27600940, 27532257, 33763395)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A new phenotype of severe dilated cardiomyopathy associated with a mutation in the LAMP2 gene previously known to cause hypertrophic cardiomyopathy in the context of Danon disease.	Gourzi P	European journal of medical genetics	2019	PMID: 29753918
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.	Walsh R	Genetics in medicine : official journal of the American College of Medical Genetics	2017	PMID: 27532257
Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.	Alfares AA	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25611685
Danon disease: further clinical and molecular heterogeneity.	Sabourdy F	Muscle & nerve	2009	PMID: 19373884
Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy.	Maron BJ	JAMA	2009	PMID: 19318653
Danon disease: an unusual presentation of autism.	Burusnukul P	Pediatric neurology	2008	PMID: 18555174
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
Phenotypic heterogeneity in two unrelated Danon patients associated with the same LAMP-2 gene mutation.	Bertini E	Neuropediatrics	2005	PMID: 16217705
Glycogen storage diseases presenting as hypertrophic cardiomyopathy.	Arad M	The New England journal of medicine	2005	PMID: 15673802
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098

Submissions - Functional Data

functionally abnormal -- retained intron

assessed by RNAseq

Result:

read abundance - intron inclusion (p=0.004)

Modifies a natural donor site at NC_000023.10:g.119576453 from 7.44 to 4.43 bits. Significant p-values: read abundance - intron inclusion (91 reads, p=0.004). 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: SCV006984412.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-DJ-A1QF), 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: Thyroid cancer, nonmedullary, 1
Transcript, protein change: NM_002294.3:c.928G>A, V310I
Molecular phenotype measured: splicing
Cell line: TCGA-DJ-A1QF
Tissue: Thyroid Carcinoma (THCA)
Collection method: in vitro
Species: human
Number of controls: 516

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.047)

Modifies a natural donor site at NC_000023.10:g.119576453 from 7.44 to 4.43 bits. Significant p-values: junction spanning - intron inclusion (4 reads, p=0.047). 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: SCV006984413.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-DJ-A3US), 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: Thyroid cancer, nonmedullary, 1
Transcript, protein change: NM_002294.3:c.928G>A, V310I
Molecular phenotype measured: splicing
Cell line: TCGA-DJ-A3US
Tissue: Thyroid Carcinoma (THCA)
Collection method: in vitro
Species: human
Number of controls: 516

functionally abnormal -- skipped exon

assessed by RNAseq

Result:

junction spanning - exon skipping (p=0.0005)

Modifies a natural donor site at NC_000023.10:g.119576453 from 7.44 to 4.43 bits. Significant p-values: junction spanning - exon skipping (1 reads, p=0.0005). 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: SCV006984414.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-BJ-A2N9), 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: Thyroid cancer, nonmedullary, 1
Transcript, protein change: NM_002294.3:c.928G>A, V310I
Molecular phenotype measured: splicing
Cell line: TCGA-BJ-A2N9
Tissue: Thyroid Carcinoma (THCA)
Collection method: in vitro
Species: human
Number of controls: 516

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0049)

Modifies a natural donor site at NC_000023.10:g.119576453 from 7.44 to 4.43 bits. Significant p-values: junction spanning - intron inclusion (6 reads, p=0.0049). 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: SCV006984415.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-DJ-A3V7), 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: Thyroid cancer, nonmedullary, 1
Transcript, protein change: NM_002294.3:c.928G>A, V310I
Molecular phenotype measured: splicing
Cell line: TCGA-DJ-A3V7
Tissue: Thyroid Carcinoma (THCA)
Collection method: in vitro
Species: human
Number of controls: 516

functionally abnormal -- skipped exon

assessed by RNAseq

Result:

junction spanning - exon skipping (p=0.0)

Modifies a natural donor site at NC_000023.10:g.119576453 from 7.44 to 4.43 bits. Significant p-values: junction spanning - exon skipping (6 reads, p=0.0). 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: SCV006984416.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-DJ-A1QM), 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: Thyroid cancer, nonmedullary, 1
Transcript, protein change: NM_002294.3:c.928G>A, V310I
Molecular phenotype measured: splicing
Cell line: TCGA-DJ-A1QM
Tissue: Thyroid Carcinoma (THCA)
Collection method: in vitro
Species: human
Number of controls: 516

Text-mined citations for rs104894858 ...

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 Apr 13, 2026