NM_016203.4(PRKAG2):c.320C>T (p.Pro107Leu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 24, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000159026.5

Allele description [Variation Report for NM_016203.4(PRKAG2):c.320C>T (p.Pro107Leu)]

NM_016203.4(PRKAG2):c.320C>T (p.Pro107Leu)

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.320C>T (p.Pro107Leu)

Other names:

p.P107L:CCG>CTG; p.Pro107Leu

HGVS:

NC_000007.14:g.151781298G>A
NG_007486.2:g.100934C>T
NM_001040633.2:c.188C>T
NM_016203.4:c.320C>TMANE SELECT
NP_001035723.1:p.Pro63Leu
NP_057287.2:p.Pro107Leu
LRG_430t1:c.320C>T
LRG_430:g.100934C>T
LRG_430p1:p.Pro107Leu
NC_000007.13:g.151478384G>A
NG_007486.1:g.100933C>T
NM_016203.3:c.320C>T

Protein change:

P107L

Links:

dbSNP: rs730880985

NCBI 1000 Genomes Browser:

rs730880985

Molecular consequence:

NM_001040633.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.320C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000208968	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jul 24, 2013)	germline	clinical testing	Citation Link,
SCV002540915	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 24, 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

SCV000208968

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jul 24, 2013)

germline

clinical testing

Citation Link,

SCV002540915

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 24, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000208968.10

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

Description

p.Pro107Leu (CCG>CTG): c.320 C>T in exon 3 of the PRKAG2 gene (NM_016203.3) The Pro107Leu variant in the PRKAG2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The Pro107Leu variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Pro107Leu represents a semi-conservative amino acid substitution resulting in the removal of a sterically-constrained Proline at a position that is conserved in mammal species. In silico analysis predicts Pro107Leu is damaging to the protein structure/function. However, mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change.With the clinical and molecular information available at this time, we cannot definitively determine if Pro107Leu is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s).

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV002540915.1

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

#	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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