VCV002862263.2 - ClinVar

NM_016203.4(PRKAG2):c.1289T>G (p.Ile430Arg)

Germline

Classification

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

Uncertain significance

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_016203.4(PRKAG2):c.1289T>G (p.Ile430Arg)

Variation ID: 2862263 Accession: VCV002862263.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q36.1 7: 151565830 (GRCh38) [ NCBI UCSC ] 7: 151262916 (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	Feb 20, 2024	Mar 4, 2025	May 5, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_016203.4:c.1289T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057287.2:p.Ile430Arg	missense
NM_001040633.2:c.1157T>G	NP_001035723.1:p.Ile386Arg	missense
NM_001304527.2:c.914T>G	NP_001291456.1:p.Ile305Arg	missense
NM_001304531.2:c.566T>G	NP_001291460.1:p.Ile189Arg	missense
NM_001363698.2:c.917T>G	NP_001350627.1:p.Ile306Arg	missense
NM_001407021.1:c.1289T>G	NP_001393950.1:p.Ile430Arg	missense
NM_001407022.1:c.1286T>G	NP_001393951.1:p.Ile429Arg	missense
NM_001407023.1:c.1286T>G	NP_001393952.1:p.Ile429Arg	missense
NM_001407024.1:c.1157T>G	NP_001393953.1:p.Ile386Arg	missense
NM_001407026.1:c.1154T>G	NP_001393955.1:p.Ile385Arg	missense
NM_001407027.1:c.1154T>G	NP_001393956.1:p.Ile385Arg	missense
NM_001407028.1:c.917T>G	NP_001393957.1:p.Ile306Arg	missense
NM_001407029.1:c.914T>G	NP_001393958.1:p.Ile305Arg	missense
NM_001407030.1:c.1001T>G	NP_001393959.1:p.Ile334Arg	missense
NM_001407031.1:c.998T>G	NP_001393960.1:p.Ile333Arg	missense
NM_001407032.1:c.971T>G	NP_001393961.1:p.Ile324Arg	missense
NM_001407033.1:c.965T>G	NP_001393962.1:p.Ile322Arg	missense
NM_001407034.1:c.566T>G	NP_001393963.1:p.Ile189Arg	missense
NM_001407035.1:c.566T>G	NP_001393964.1:p.Ile189Arg	missense
NM_001407036.1:c.563T>G	NP_001393965.1:p.Ile188Arg	missense
NM_001407037.1:c.626T>G	NP_001393966.1:p.Ile209Arg	missense
NM_001407038.1:c.614T>G	NP_001393967.1:p.Ile205Arg	missense
NM_001407039.1:c.563T>G	NP_001393968.1:p.Ile188Arg	missense
NM_001407040.1:c.563T>G	NP_001393969.1:p.Ile188Arg	missense
NM_024429.2:c.566T>G	NP_077747.1:p.Ile189Arg	missense
NC_000007.14:g.151565830A>C
NC_000007.13:g.151262916A>C
NG_007486.2:g.316402T>G
LRG_430:g.316402T>G
LRG_430t1:c.1289T>G	LRG_430p1:p.Ile430Arg

... more HGVS ... less HGVS

Protein change

I188R, I189R, I306R, I385R, I386R, I305R, I429R, I430R, I322R, I324R, I334R, I205R, I209R, I333R

Other names

Canonical SPDI

NC_000007.14:151565829: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: CA370071094 dbSNP: rs2536297089 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.
PRKAG2		No evidence available	No evidence available	GRCh38 GRCh37	1292	1489

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.
Lethal congenital glycogen storage disease of heart	Uncertain significance (1)	criteria provided, single submitter	May 5, 2023	RCV003617590.3

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 (May 05, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Lethal congenital glycogen storage disease of heart	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004462120.2 First in ClinVar: Feb 20, 2024 Last updated: Mar 04, 2025	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 expected to disrupt PRKAG2 protein function. This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 430 of the PRKAG2 protein (p.Ile430Arg). (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 expected to disrupt PRKAG2 protein function. This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 430 of the PRKAG2 protein (p.Ile430Arg).

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 rs2536297089 ...

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 May 19, 2025