VCV001013076.12 - ClinVar

NM_002294.3(LAMP2):c.331A>G (p.Ile111Val)

Germline

Classification

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

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

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.331A>G (p.Ile111Val)

Variation ID: 1013076 Accession: VCV001013076.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120455423 (GRCh38) [ NCBI UCSC ] X: 119589278 (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	Mar 14, 2021	Jul 13, 2025	May 16, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.331A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Ile111Val	missense
NM_001122606.1:c.331A>G	NP_001116078.1:p.Ile111Val	missense
NM_002294.2:c.331A>G
NM_013995.2:c.331A>G	NP_054701.1:p.Ile111Val	missense
NC_000023.11:g.120455423T>C
NC_000023.10:g.119589278T>C
NG_007995.1:g.18927A>G
LRG_749:g.18927A>G
LRG_749t1:c.331A>G
LRG_749t2:c.331A>G	LRG_749p2:p.Ile111Val
LRG_749t3:c.331A>G	LRG_749p3:p.Ile111Val

... more HGVS ... less HGVS

Protein change

I111V

Other names

Canonical SPDI

NC_000023.11:120455422: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.

0.00026 (C)

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

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

1000 Genomes Project 30x 0.00021

1000 Genomes Project 0.00026

Links

ClinGen: CA10505321 dbSNP: rs762218821 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 (1)	criteria provided, single submitter	Apr 1, 2023	RCV001871775.11
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	May 16, 2025	RCV005590016.1

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 (Apr 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002277730.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024	Comment: show 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMP2 protein function. ClinVar contains an entry for this variant (Variation ID: 1013076). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is present in population databases (rs762218821, gnomAD 0.001%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 111 of the LAMP2 protein (p.Ile111Val). (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

Likely benign (May 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV006266187.1 First in ClinVar: Jul 13, 2025 Last updated: Jul 13, 2025	Publications: PubMed (1) PubMed: 33495597 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

Comment:

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMP2 protein function. ClinVar contains an entry for this variant (Variation ID: 1013076). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is present in population databases (rs762218821, gnomAD 0.001%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 111 of the LAMP2 protein (p.Ile111Val).

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.	Harper AR	Nature genetics	2021	PMID: 33495597

Text-mined citations for rs762218821 ...

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