NM_016203.4(PRKAG2):c.1355T>C (p.Phe452Ser) AND Lethal congenital glycogen storage disease of heart

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 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:: RCV002996170.3

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1355T>C (p.Phe452Ser)]

NM_016203.4(PRKAG2):c.1355T>C (p.Phe452Ser)

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.1355T>C (p.Phe452Ser)

HGVS:

NC_000007.14:g.151565764A>G
NG_007486.2:g.316468T>C
NM_001040633.2:c.1223T>C
NM_001304527.2:c.980T>C
NM_001304531.2:c.632T>C
NM_001363698.2:c.983T>C
NM_001407021.1:c.1355T>C
NM_001407022.1:c.1352T>C
NM_001407023.1:c.1352T>C
NM_001407024.1:c.1223T>C
NM_001407026.1:c.1220T>C
NM_001407027.1:c.1220T>C
NM_001407028.1:c.983T>C
NM_001407029.1:c.980T>C
NM_001407030.1:c.1067T>C
NM_001407031.1:c.1064T>C
NM_001407032.1:c.1037T>C
NM_001407033.1:c.1031T>C
NM_001407034.1:c.632T>C
NM_001407035.1:c.632T>C
NM_001407036.1:c.629T>C
NM_001407037.1:c.692T>C
NM_001407038.1:c.680T>C
NM_001407039.1:c.629T>C
NM_001407040.1:c.629T>C
NM_016203.4:c.1355T>CMANE SELECT
NM_024429.2:c.632T>C
NP_001035723.1:p.Phe408Ser
NP_001291456.1:p.Phe327Ser
NP_001291460.1:p.Phe211Ser
NP_001350627.1:p.Phe328Ser
NP_001393950.1:p.Phe452Ser
NP_001393951.1:p.Phe451Ser
NP_001393952.1:p.Phe451Ser
NP_001393953.1:p.Phe408Ser
NP_001393955.1:p.Phe407Ser
NP_001393956.1:p.Phe407Ser
NP_001393957.1:p.Phe328Ser
NP_001393958.1:p.Phe327Ser
NP_001393959.1:p.Phe356Ser
NP_001393960.1:p.Phe355Ser
NP_001393961.1:p.Phe346Ser
NP_001393962.1:p.Phe344Ser
NP_001393963.1:p.Phe211Ser
NP_001393964.1:p.Phe211Ser
NP_001393965.1:p.Phe210Ser
NP_001393966.1:p.Phe231Ser
NP_001393967.1:p.Phe227Ser
NP_001393968.1:p.Phe210Ser
NP_001393969.1:p.Phe210Ser
NP_057287.2:p.Phe452Ser
NP_077747.1:p.Phe211Ser
LRG_430t1:c.1355T>C
LRG_430:g.316468T>C
LRG_430p1:p.Phe452Ser
NC_000007.13:g.151262850A>G

Protein change:

F210S

Molecular consequence:

NM_001040633.2:c.1223T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.980T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.983T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407021.1:c.1355T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407022.1:c.1352T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407023.1:c.1352T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407024.1:c.1223T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407026.1:c.1220T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407027.1:c.1220T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407028.1:c.983T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407029.1:c.980T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407030.1:c.1067T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407031.1:c.1064T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407032.1:c.1037T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407033.1:c.1031T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407034.1:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407035.1:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407036.1:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407037.1:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407038.1:c.680T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407039.1:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407040.1:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1355T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.632T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003300210	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003300210

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV003300210.2

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

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) 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 present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 452 of the PRKAG2 protein (p.Phe452Ser).

#	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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