NM_016203.4(PRKAG2):c.1007T>C (p.Val336Ala) AND Lethal congenital glycogen storage disease of heart

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 30, 2021
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:: RCV002007521.5

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1007T>C (p.Val336Ala)]

NM_016203.4(PRKAG2):c.1007T>C (p.Val336Ala)

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.1007T>C (p.Val336Ala)

HGVS:

NC_000007.14:g.151572708A>G
NG_007486.2:g.309524T>C
NM_001040633.2:c.875T>C
NM_001304527.2:c.632T>C
NM_001304531.2:c.284T>C
NM_001363698.2:c.635T>C
NM_016203.4:c.1007T>CMANE SELECT
NM_024429.2:c.284T>C
NP_001035723.1:p.Val292Ala
NP_001291456.1:p.Val211Ala
NP_001291460.1:p.Val95Ala
NP_001350627.1:p.Val212Ala
NP_057287.2:p.Val336Ala
NP_077747.1:p.Val95Ala
LRG_430t1:c.1007T>C
LRG_430:g.309524T>C
LRG_430p1:p.Val336Ala
NC_000007.13:g.151269794A>G
NG_007486.1:g.309523T>C

Protein change:

V211A

Links:

dbSNP: rs2151024166

NCBI 1000 Genomes Browser:

rs2151024166

Molecular consequence:

NM_001040633.2:c.875T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.635T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1007T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.284T>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002228001	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 30, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28546535, 28431061, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002228001

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 30, 2021)

germline

clinical testing

PubMed (3)
[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

A novel PRKAG2 mutation in a Chinese family with cardiac hypertrophy and ventricular pre-excitation.

Yang KQ, Lu CX, Zhang Y, Yang YK, Li JC, Lan T, Meng X, Fan P, Tian T, Wang LP, Liu YX, Zhang X, Zhou XL.

Sci Rep. 2017 May 25;7(1):2407. doi: 10.1038/s41598-017-02455-z.

PubMed [citation]

PMID:: 28546535
PMCID:: PMC5445094

High prevalence of arrhythmic and myocardial complications in patients with cardiac glycogenosis due to PRKAG2 mutations.

Thevenon J, Laurent G, Ader F, Laforêt P, Klug D, Duva Pentiah A, Gouya L, Maurage CA, Kacet S, Eicher JC, Albuisson J, Desnos M, Bieth E, Duboc D, Martin L, Réant P, Picard F, Bonithon-Kopp C, Gautier E, Binquet C, Thauvin-Robinet C, Faivre L, et al.

Europace. 2017 Apr 1;19(4):651-659. doi: 10.1093/europace/euw067.

PubMed [citation]

PMID:: 28431061

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002228001.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val336 amino acid residue in PRKAG2. Other variant(s) that disrupt this residue have been observed in individuals with PRKAG2-related conditions (PMID: 28546535), which suggests that this may be a clinically significant amino acid residue. This sequence change replaces valine with alanine at codon 336 of the PRKAG2 protein (p.Val336Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28431061; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated.

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine