NM_016203.4(PRKAG2):c.1184C>T (p.Ala395Val) AND Lethal congenital glycogen storage disease of heart

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 28, 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:: RCV001875936.6

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1184C>T (p.Ala395Val)]

NM_016203.4(PRKAG2):c.1184C>T (p.Ala395Val)

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.1184C>T (p.Ala395Val)

HGVS:

NC_000007.14:g.151568765G>A
NG_007486.2:g.313467C>T
NM_001040633.2:c.1052C>T
NM_001304527.2:c.809C>T
NM_001304531.2:c.461C>T
NM_001363698.2:c.812C>T
NM_016203.4:c.1184C>TMANE SELECT
NM_024429.2:c.461C>T
NP_001035723.1:p.Ala351Val
NP_001291456.1:p.Ala270Val
NP_001291460.1:p.Ala154Val
NP_001350627.1:p.Ala271Val
NP_057287.2:p.Ala395Val
NP_077747.1:p.Ala154Val
LRG_430t1:c.1184C>T
LRG_430:g.313467C>T
LRG_430p1:p.Ala395Val
NC_000007.13:g.151265851G>A
NC_000007.13:g.151265851G>A
NG_007486.1:g.313466C>T

Protein change:

A154V

Links:

dbSNP: rs1806859703

NCBI 1000 Genomes Browser:

rs1806859703

Molecular consequence:

NM_001040633.2:c.1052C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.809C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.461C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.812C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.461C>T - 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
SCV002211182	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 28, 2021)	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

SCV002211182

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 28, 2021)

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, SCV002211182.3

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

Description

This sequence change replaces alanine with valine at codon 395 of the PRKAG2 protein (p.Ala395Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. 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 not expected to disrupt PRKAG2 protein function. This variant has not been reported in the literature in individuals with PRKAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 920610). This variant is not present in population databases (ExAC no frequency).

#	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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