NM_016203.4(PRKAG2):c.1006G>A (p.Val336Ile) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 17, 2023
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:: RCV000617676.4

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1006G>A (p.Val336Ile)]

NM_016203.4(PRKAG2):c.1006G>A (p.Val336Ile)

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.1006G>A (p.Val336Ile)

Other names:

p.V336I:GTA>ATA

HGVS:

NC_000007.14:g.151572709C>T
NG_007486.2:g.309523G>A
NM_001040633.2:c.874G>A
NM_001304527.2:c.631G>A
NM_001304531.2:c.283G>A
NM_001363698.2:c.634G>A
NM_016203.4:c.1006G>AMANE SELECT
NM_024429.2:c.283G>A
NP_001035723.1:p.Val292Ile
NP_001035723.1:p.Val292Ile
NP_001291456.1:p.Val211Ile
NP_001291460.1:p.Val95Ile
NP_001350627.1:p.Val212Ile
NP_057287.2:p.Val336Ile
NP_077747.1:p.Val95Ile
LRG_430t1:c.1006G>A
LRG_430:g.309523G>A
LRG_430p1:p.Val336Ile
NC_000007.13:g.151269795C>T
NG_007486.1:g.309522G>A
NM_001040633.1:c.874G>A
NM_016203.3:c.1006G>A

Protein change:

V211I

Links:

dbSNP: rs727504707

NCBI 1000 Genomes Browser:

rs727504707

Molecular consequence:

NM_001040633.2:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.631G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.634G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1006G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000740204	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27532257, 28431061, 28546535 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000740204

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 17, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

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 Ambry Genetics, SCV000740204.6

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

Description

The p.V336I variant (also known as c.1006G>A) is located in coding exon 9 of the PRKAG2 gene. The valine at codon 336 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 9. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Walsh R et al. Genet. Med., 2017 Feb;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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