VCV000044430.37 - ClinVar

NM_002294.3(LAMP2):c.517G>A (p.Val173Ile)

Germline

Classification

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

Conflicting classifications of pathogenicity
Uncertain significance (1); Likely benign (4)

5 out of 5 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.517G>A (p.Val173Ile)

Variation ID: 44430 Accession: VCV000044430.37

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120449009 (GRCh38) [ NCBI UCSC ] X: 119582864 (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 8, 2017	Jul 27, 2026	Oct 26, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.517G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Val173Ile	missense
NM_001122606.1:c.517G>A	NP_001116078.1:p.Val173Ile	missense
NM_013995.2:c.517G>A	NP_054701.1:p.Val173Ile	missense
NC_000023.11:g.120449009C>T
NC_000023.10:g.119582864C>T
NG_007995.1:g.25341G>A
LRG_749:g.25341G>A
LRG_749t1:c.517G>A	LRG_749p1:p.Val173Ile
LRG_749t2:c.517G>A	LRG_749p2:p.Val173Ile
LRG_749t3:c.517G>A	LRG_749p3:p.Val173Ile

... more HGVS ... less HGVS

Protein change

V173I

Other names

Canonical SPDI

NC_000023.11:120449008: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.

Exome Aggregation Consortium (ExAC) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00003

The Genome Aggregation Database (gnomAD) 0.00004

The Genome Aggregation Database (gnomAD) 0.00005

Trans-Omics for Precision Medicine (TOPMed) 0.00006

The Genome Aggregation Database (gnomAD), exomes 0.00008

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00019

Links

ClinGen: CA134133 dbSNP: rs141574558 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.
not specified	Uncertain significance (1)	criteria provided, single submitter	Feb 28, 2014	RCV000037420.7
Danon disease	Likely benign (1)	criteria provided, single submitter	Oct 26, 2025	RCV000638586.11
not provided	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 1, 2024	RCV001697132.22
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Nov 8, 2019	RCV002336130.2

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.
Uncertain significance (Feb 28, 2014) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000061077.5 First in ClinVar: May 03, 2013 Last updated: Mar 08, 2017	Comment: show Variant classified as Uncertain Significance - Favor Benign. The Val173Ile varia nt in LAMP2 has been previously reported by our laboratory in 2 individuals with HCM who were also carriers of a pathogenic variant in another HCM gene. It has also been identified in 2/6728 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbSNP rs141574558). Computati onal prediction tools suggest that this variant may not impact the protein, thou gh this information is not predictive enough to rule out pathogenicity. Valine ( Val) at position 173 is not conserved in mammals or evolutionarily distant speci es, with one mammal (Chinese tree shrew) and some fish having this variant (Ile) at this position, further supporting that a change at this position may be tole rated. Furthermore, nearly all disease-causing variants in LAMP2 have been trunc ating, while this is a missense variant. In summary, although this data supports that the Val173Ile variant may be more likely benign, additional studies are ne eded to fully assess its clinical significance. (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: 5

Likely benign (Nov 15, 2019) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000532767.5 First in ClinVar: Mar 08, 2017 Last updated: Sep 25, 2021	Comment: show This variant is associated with the following publications: (PMID: 27532257) (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 (Nov 08, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002644140.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 27532257 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 (Oct 26, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000760118.8 First in ClinVar: May 28, 2018 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

Likely benign (Jan 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004701180.21 First in ClinVar: Mar 10, 2024 Last updated: Jul 27, 2026	Comment: show LAMP2: BP4, BS2 (less) 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 Number of individuals with the variant: 1

Comment:

Variant classified as Uncertain Significance - Favor Benign. The Val173Ile varia nt in LAMP2 has been previously reported by our laboratory in 2 individuals with HCM who were also carriers of a pathogenic variant in another HCM gene. It has also been identified in 2/6728 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbSNP rs141574558). Computati onal prediction tools suggest that this variant may not impact the protein, thou gh this information is not predictive enough to rule out pathogenicity. Valine ( Val) at position 173 is not conserved in mammals or evolutionarily distant speci es, with one mammal (Chinese tree shrew) and some fish having this variant (Ile) at this position, further supporting that a change at this position may be tole rated. Furthermore, nearly all disease-causing variants in LAMP2 have been trunc ating, while this is a missense variant. In summary, although this data supports that the Val173Ile variant may be more likely benign, additional studies are ne eded to fully assess its clinical significance.

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
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

Text-mined citations for rs141574558 ...

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 Jul 27, 2026