NM_002693.3(POLG):c.2255T>C (p.Leu752Pro) AND POLG-Related Spectrum Disorders

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 18, 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:: RCV001796438.4

Allele description [Variation Report for NM_002693.3(POLG):c.2255T>C (p.Leu752Pro)]

NM_002693.3(POLG):c.2255T>C (p.Leu752Pro)

Gene:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.2255T>C (p.Leu752Pro)

HGVS:

NC_000015.10:g.89323414A>G
NG_008218.2:g.16382T>C
NM_001126131.2:c.2255T>C
NM_002693.3:c.2255T>CMANE SELECT
NP_001119603.1:p.Leu752Pro
NP_002684.1:p.Leu752Pro
LRG_765:g.16382T>C
NC_000015.9:g.89866645A>G

Protein change:

L752P

Links:

dbSNP: rs2055426653

NCBI 1000 Genomes Browser:

rs2055426653

Molecular consequence:

NM_001126131.2:c.2255T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.2255T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: POLG-Related Spectrum Disorders
Identifiers:: MedGen: C4763519

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002034801	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020)	Uncertain significance (Nov 18, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18716558, 21824913 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002034801

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)

Uncertain significance
(Nov 18, 2021)

unknown

clinical testing

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clonally expanded mitochondrial DNA mutations in epileptic individuals with mutated DNA polymerase gamma.

Zsurka G, Baron M, Stewart JD, Kornblum C, Bös M, Sassen R, Taylor RW, Elger CE, Chinnery PF, Kunz WS.

J Neuropathol Exp Neurol. 2008 Sep;67(9):857-66. doi: 10.1097/NEN.0b013e3181839b2d.

PubMed [citation]

PMID:: 18716558

Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol γ.

Euro L, Farnum GA, Palin E, Suomalainen A, Kaguni LS.

Nucleic Acids Res. 2011 Nov;39(21):9072-84. doi: 10.1093/nar/gkr618. Epub 2011 Aug 8. Review.

PubMed [citation]

PMID:: 21824913
PMCID:: PMC3241644

Details of each submission

From Illumina Laboratory Services, Illumina, SCV002034801.1

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

Description

The POLG c.2255T>C (p.Leu752Pro) variant is a missense variant. This variant has been reported in a compound heterozygous state with a complex allele in a 7-year old female with complex partial seizures, migraine, VPA-induced liver failure and reduced mitochondrial DNA copy number in blood, who died at 10 years (Zsurka et al. 2008). This variant is not found in the Genome Aggregation Database version 2.1.1 or 3.1.2 in a region of good sequence coverage, so the variant is presumed to be rare. The Gly763 residue is located in the spacer domain, which is involved in binding to DNA (Euro et al. 2011). Based on the limited evidence, the p.Leu752Pro variant is classified as a variant of uncertain significance for POLG-related spectrum disorders.

#	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

Last Updated: Oct 8, 2024

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