VCV000578311.15 - ClinVar

NM_002294.3(LAMP2):c.443A>G (p.Asn148Ser)

Germline

Classification

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

Conflicting classifications of pathogenicity
Uncertain significance (3); Likely benign (1)

4 out of 4 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.443A>G (p.Asn148Ser)

Variation ID: 578311 Accession: VCV000578311.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120449083 (GRCh38) [ NCBI UCSC ] X: 119582938 (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	Oct 10, 2018	Mar 7, 2026	Nov 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.443A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Asn148Ser	missense
NM_001122606.1:c.443A>G	NP_001116078.1:p.Asn148Ser	missense
NM_013995.2:c.443A>G	NP_054701.1:p.Asn148Ser	missense
NC_000023.11:g.120449083T>C
NC_000023.10:g.119582938T>C
NG_007995.1:g.25267A>G
LRG_749:g.25267A>G
LRG_749t1:c.443A>G	LRG_749p1:p.Asn148Ser
LRG_749t2:c.443A>G	LRG_749p2:p.Asn148Ser
LRG_749t3:c.443A>G	LRG_749p3:p.Asn148Ser

... more HGVS ... less HGVS

Protein change

N148S

Other names

Canonical SPDI

NC_000023.11:120449082: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.

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

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00002

The Genome Aggregation Database (gnomAD) 0.00005

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD) 0.00006

Links

ClinGen: CA10505302 dbSNP: rs766491800 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	1133

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	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Nov 3, 2025	RCV000701278.9
not provided	Uncertain significance (1)	criteria provided, single submitter	Apr 2, 2025	RCV001561766.3
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Aug 22, 2024	RCV002332480.4

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.
Uncertain significance (Aug 11, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Danon disease	Fulgent Genetics, Fulgent Genetics Accession: SCV002788695.1 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 (Aug 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002632282.4 First in ClinVar: Nov 29, 2022 Last updated: Jan 13, 2025	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (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

Uncertain significance (Apr 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001784424.2 First in ClinVar: Aug 14, 2021 Last updated: Apr 20, 2025	Comment: show Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function (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

Uncertain significance (Nov 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000830070.7 First in ClinVar: Oct 10, 2018 Last updated: Mar 07, 2026	Publications: PubMed (1) PubMed: 28492532 Comment: show This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 148 of the LAMP2 protein (p.Asn148Ser). This variant is present in population databases (rs766491800, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. 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: 578311). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LAMP2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 148 of the LAMP2 protein (p.Asn148Ser). This variant is present in population databases (rs766491800, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. 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: 578311). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LAMP2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs766491800 ...

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