VCV000463159.11 - ClinVar

NM_002294.3(LAMP2):c.696T>A (p.Cys232Ter)

Germline

Classification

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

Pathogenic

2 out of 2 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_002294.3(LAMP2):c.696T>A (p.Cys232Ter)

Variation ID: 463159 Accession: VCV000463159.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120447886 (GRCh38) [ NCBI UCSC ] X: 119581741 (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	Dec 26, 2017	Feb 23, 2026	Oct 18, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.696T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Cys232Ter	nonsense
NM_001122606.1:c.696T>A	NP_001116078.1:p.Cys232Ter	nonsense
NM_013995.2:c.696T>A	NP_054701.1:p.Cys232Ter	nonsense
NC_000023.11:g.120447886A>T
NC_000023.10:g.119581741A>T
NG_007995.1:g.26464T>A
LRG_749:g.26464T>A
LRG_749t1:c.696T>A	LRG_749p1:p.Cys232Ter
LRG_749t2:c.696T>A	LRG_749p2:p.Cys232Ter
LRG_749t3:c.696T>A	LRG_749p3:p.Cys232Ter

... more HGVS ... less HGVS

Protein change

C232*

Other names

Canonical SPDI

NC_000023.11:120447885:A: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: CA414401297 dbSNP: rs1556101523 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	942	1118

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 (1)	criteria provided, single submitter	Oct 18, 2024	RCV000549262.9
Cardiovascular phenotype	Pathogenic (1)	criteria provided, single submitter	Jan 3, 2023	RCV003159800.2

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 (Jan 03, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV003853685.2 First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024	Comment: show The p.C232* pathogenic mutation (also known as c.696T>A), located in coding exon 5 of the LAMP2 gene, results from a T to A substitution at nucleotide position 696. This changes the amino acid from a cysteine to a stop codon within coding exon 5. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, 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 (Oct 18, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000636867.9 First in ClinVar: Dec 26, 2017 Last updated: Feb 23, 2026	Publications: PubMed (1) PubMed: 21415759 Comment: show This sequence change creates a premature translational stop signal (p.Cys232*) in the LAMP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 463159). 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

Comment:

The p.C232* pathogenic mutation (also known as c.696T>A), located in coding exon 5 of the LAMP2 gene, results from a T to A substitution at nucleotide position 696. This changes the amino acid from a cysteine to a stop codon within coding exon 5. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

This sequence change creates a premature translational stop signal (p.Cys232*) in the LAMP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 463159). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Natural history of Danon disease.	Boucek D	Genetics in medicine : official journal of the American College of Medical Genetics	2011	PMID: 21415759

Text-mined citations for rs1556101523 ...

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 Feb 24, 2026