NM_016203.4(PRKAG2):c.1361A>G (p.Glu454Gly) AND Lethal congenital glycogen storage disease of heart

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 4, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002559183.3

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1361A>G (p.Glu454Gly)]

NM_016203.4(PRKAG2):c.1361A>G (p.Glu454Gly)

Gene:

PRKAG2:protein kinase AMP-activated non-catalytic subunit gamma 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_016203.4(PRKAG2):c.1361A>G (p.Glu454Gly)

HGVS:

NC_000007.14:g.151565758T>C
NG_007486.2:g.316474A>G
NM_001040633.2:c.1229A>G
NM_001304527.2:c.986A>G
NM_001304531.2:c.638A>G
NM_001363698.2:c.989A>G
NM_016203.4:c.1361A>GMANE SELECT
NM_024429.2:c.638A>G
NP_001035723.1:p.Glu410Gly
NP_001291456.1:p.Glu329Gly
NP_001291460.1:p.Glu213Gly
NP_001350627.1:p.Glu330Gly
NP_057287.2:p.Glu454Gly
NP_077747.1:p.Glu213Gly
LRG_430t1:c.1361A>G
LRG_430:g.316474A>G
LRG_430p1:p.Glu454Gly
NC_000007.13:g.151262844T>C
NC_000007.13:g.151262844T>C
NG_007486.1:g.316473A>G

Protein change:

E213G

Links:

dbSNP: rs940818676

NCBI 1000 Genomes Browser:

rs940818676

Molecular consequence:

NM_001040633.2:c.1229A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.986A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.638A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.989A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1361A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.638A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lethal congenital glycogen storage disease of heart
Synonyms:: GLYCOGEN STORAGE DISEASE OF HEART; PHOSPHORYLASE KINASE DEFICIENCY OF HEART
Identifiers:: MONDO: MONDO:0009867; MedGen: C1849813; Orphanet: 439854; OMIM: 261740

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003253174	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32646569, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003253174

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 4, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis.

Lopez-Sainz A, Dominguez F, Lopes LR, Ochoa JP, Barriales-Villa R, Climent V, Linschoten M, Tiron C, Chiriatti C, Marques N, Rasmussen TB, Espinosa MÁ, Beinart R, Quarta G, Cesar S, Field E, Garcia-Pinilla JM, Bilinska Z, Muir AR, Roberts AM, Santas E, Zorio E, et al.

J Am Coll Cardiol. 2020 Jul 14;76(2):186-197. doi: 10.1016/j.jacc.2020.05.029.

PubMed [citation]

PMID:: 32646569

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003253174.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKAG2 protein function. ClinVar contains an entry for this variant (Variation ID: 927650). This missense change has been observed in individual(s) with PRKAG2-related conditions (PMID: 32646569). This variant is present in population databases (no rsID available, gnomAD 0.1%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 454 of the PRKAG2 protein (p.Glu454Gly).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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