NM_002693.3(POLG):c.408C>G (p.Asp136Glu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Apr 27, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000514076.19

Allele description [Variation Report for NM_002693.3(POLG):c.408C>G (p.Asp136Glu)]

NM_002693.3(POLG):c.408C>G (p.Asp136Glu)

Genes:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.408C>G (p.Asp136Glu)

Other names:

p.D136E:GAC>GAG

HGVS:

NC_000015.10:g.89333347G>C
NG_008218.2:g.6449C>G
NM_001126131.2:c.408C>G
NM_002693.3:c.408C>GMANE SELECT
NP_001119603.1:p.Asp136Glu
NP_002684.1:p.Asp136Glu
NP_002684.1:p.Asp136Glu
LRG_765t1:c.408C>G
LRG_765:g.6449C>G
LRG_765p1:p.Asp136Glu
NC_000015.9:g.89876578G>C
NM_002693.2:c.408C>G
p.Asp136Glu

Protein change:

D136E

Links:

dbSNP: rs115109291

NCBI 1000 Genomes Browser:

rs115109291

Molecular consequence:

NM_001126131.2:c.408C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.408C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000242256	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jan 26, 2021)	germline	clinical testing	Citation Link,
SCV000340284	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Aug 29, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19578034, 21880868 Citation Link,
SCV000610955	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 17, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001145166	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics criteria)	Uncertain significance (May 13, 2021)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19578034, 21880868, 26467025
SCV001716244	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19578034, 21880868, 24508722, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	13	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

The unfolding clinical spectrum of POLG mutations.

Blok MJ, van den Bosch BJ, Jongen E, Hendrickx A, de Die-Smulders CE, Hoogendijk JE, Brusse E, de Visser M, Poll-The BT, Bierau J, de Coo IF, Smeets HJ.

J Med Genet. 2009 Nov;46(11):776-85. doi: 10.1136/jmg.2009.067686. Epub 2009 Jul 2.

PubMed [citation]

PMID:: 19578034

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000242256.14

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

Description

Observed as heterozygous in two siblings with epilepsy and was considered by the authors to be a variant of unknown clinical significance (Blok et al., 2009).; This variant is associated with the following publications: (PMID: 24508722, 21880868, 19578034)

#	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 Eurofins Ntd Llc (ga), SCV000340284.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	clinical testing	PubMed (2)

#	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		10	not provided	not provided	not provided

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000610955.1

#	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	not provided	not provided	not provided	not provided		not provided	0.000347	not provided	not provided

From Athena Diagnostics Inc, SCV001145166.2

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

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001716244.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

BP4

#	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		3	not provided	not provided	not provided

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine