VCV000044431.4 - ClinVar

NM_002294.3(LAMP2):c.56T>G (p.Leu19Arg)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (1)

This classification is based on the single submission received

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.56T>G (p.Leu19Arg)

Variation ID: 44431 Accession: VCV000044431.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120469114 (GRCh38) [ NCBI UCSC ] X: 119602969 (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	Jan 31, 2015	Jan 31, 2015	Feb 3, 2011

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.56T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Leu19Arg	missense
NM_001122606.1:c.56T>G	NP_001116078.1:p.Leu19Arg	missense
NM_013995.2:c.56T>G	NP_054701.1:p.Leu19Arg	missense
NC_000023.11:g.120469114A>C
NC_000023.10:g.119602969A>C
NG_007995.1:g.5236T>G
LRG_749:g.5236T>G
LRG_749t1:c.56T>G	LRG_749p1:p.Leu19Arg
LRG_749t2:c.56T>G	LRG_749p2:p.Leu19Arg
LRG_749t3:c.56T>G	LRG_749p3:p.Leu19Arg

... more HGVS ... less HGVS

Protein change

L19R

Other names

Canonical SPDI

NC_000023.11:120469113:A: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.

Links

ClinGen: CA134140 dbSNP: rs397516745 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 3, 2011	RCV000037421.5

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 03, 2011) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000061078.5 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Comment: show Variant classified as Uncertain Significance - Favor Pathogenic. The Leu19Arg va riant has not been reported in the literature and has not been previously detect ed in over 2000 Caucasian chromosomes tested at our laboratory. This low freque ncy supports a pathogenic role as does the fact that it was detected in an indiv idual with a clinical presentation and family history consistent with Danon dise ase. However, although leucine (Leu) at position 19 is conserved among many mam malian species as well as more distant species (chicken, frog), one mammalian sp ecies (elephant) carries a different amino acid, reducing the likelihood that th e change is pathogenic. Importantly, pathogenic missense variants are very rare in the LAMP2 gene (most disease causing variants cause a loss of function). In summary, additional evidence is needed to determine the significance of this var iant. (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: 1

Comment:

Variant classified as Uncertain Significance - Favor Pathogenic. The Leu19Arg va riant has not been reported in the literature and has not been previously detect ed in over 2000 Caucasian chromosomes tested at our laboratory. This low freque ncy supports a pathogenic role as does the fact that it was detected in an indiv idual with a clinical presentation and family history consistent with Danon dise ase. However, although leucine (Leu) at position 19 is conserved among many mam malian species as well as more distant species (chicken, frog), one mammalian sp ecies (elephant) carries a different amino acid, reducing the likelihood that th e change is pathogenic. Importantly, pathogenic missense variants are very rare in the LAMP2 gene (most disease causing variants cause a loss of function). In summary, additional evidence is needed to determine the significance of this var iant.

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 rs397516745 ...

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 Dec 24, 2022