VCV000180866.18 - ClinVar

NM_002294.3(LAMP2):c.797G>A (p.Arg266His)

Germline

Classification

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

Benign/Likely benign
Benign (1); Likely benign (3)

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.797G>A (p.Arg266His)

Variation ID: 180866 Accession: VCV000180866.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120446372 (GRCh38) [ NCBI UCSC ] X: 119580227 (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	May 29, 2016	Sep 5, 2026	Jun 9, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.797G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Arg266His	missense
NM_001122606.1:c.797G>A	NP_001116078.1:p.Arg266His	missense
NM_013995.2:c.797G>A	NP_054701.1:p.Arg266His	missense
NC_000023.11:g.120446372C>T
NC_000023.10:g.119580227C>T
NG_007995.1:g.27978G>A
LRG_749:g.27978G>A
LRG_749t1:c.797G>A	LRG_749p1:p.Arg266His
LRG_749t2:c.797G>A	LRG_749p2:p.Arg266His
LRG_749t3:c.797G>A	LRG_749p3:p.Arg266His

... more HGVS ... less HGVS

Protein change

R266H

Other names

p.R266H:CGT>CAT

Canonical SPDI

NC_000023.11:120446371: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.

0.00026 (T)

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

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD) 0.00002

Exome Aggregation Consortium (ExAC) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00009

1000 Genomes Project 30x 0.00021

1000 Genomes Project 0.00026

Links

ClinGen: CA333625 dbSNP: rs200934351 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.
not provided	Likely benign (1)	criteria provided, single submitter	Mar 26, 2019	RCV000157957.5
Danon disease	Benign (1)	criteria provided, single submitter	Jan 14, 2026	RCV001078726.10
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Jan 18, 2025	RCV002415690.3
not specified	Likely benign (1)	criteria provided, single submitter	Jun 9, 2026	RCV006752530.1

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.
Likely benign (Mar 26, 2019) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000207892.12 First in ClinVar: Feb 24, 2015 Last updated: May 29, 2016	Comment: show This variant is associated with the following publications: (PMID: 31983221) (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

Likely benign (Jan 18, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002681641.3 First in ClinVar: Nov 29, 2022 Last updated: Apr 28, 2025	Publications: PubMed (1) PubMed: 31983221 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

Likely benign (Jun 09, 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: SCV007671484.1 First in ClinVar: Sep 05, 2026 Last updated: Sep 05, 2026	Publications: PubMed (1) PubMed: 31983221 Comment: show Variant summary: LAMP2 c.797G>A (p.Arg266His) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 7.1e-05 in 183372 control chromosomes. The observed variant frequency exceeds the estimated maximal expected allele frequency for disease-causing variants in LAMP2. c.797G>A has been observed in an individual affected with Dilated Cardiomyopathy (Mazzarotto_2020). This report does not provide unequivocal conclusions about association of the variant with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 180866). Based on the evidence outlined above, the variant was classified as likely benign. (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

Benign (Jan 14, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001010120.8 First in ClinVar: Dec 17, 2019 Last updated: Feb 15, 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

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:

Variant summary: LAMP2 c.797G>A (p.Arg266His) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 7.1e-05 in 183372 control chromosomes. The observed variant frequency exceeds the estimated maximal expected allele frequency for disease-causing variants in LAMP2. c.797G>A has been observed in an individual affected with Dilated Cardiomyopathy (Mazzarotto_2020). This report does not provide unequivocal conclusions about association of the variant with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 180866). Based on the evidence outlined above, the variant was classified as likely benign.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.	Mazzarotto F	Circulation	2020	PMID: 31983221

Text-mined citations for rs200934351 ...

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 05, 2026