NM_002693.3(POLG):c.679C>T (p.Arg227Trp) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 27, 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:: RCV002513044.2

Allele description [Variation Report for NM_002693.3(POLG):c.679C>T (p.Arg227Trp)]

NM_002693.3(POLG):c.679C>T (p.Arg227Trp)

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.679C>T (p.Arg227Trp)

HGVS:

NC_000015.10:g.89330257G>A
NG_008218.2:g.9539C>T
NM_001126131.2:c.679C>T
NM_002693.3:c.679C>TMANE SELECT
NP_001119603.1:p.Arg227Trp
NP_002684.1:p.Arg227Trp
NP_002684.1:p.Arg227Trp
LRG_765t1:c.679C>T
LRG_765:g.9539C>T
LRG_765p1:p.Arg227Trp
NC_000015.9:g.89873488G>A
NM_002693.2:c.679C>T
P54098:p.Arg227Trp

Protein change:

R227W; ARG227TRP

Links:

UniProtKB: P54098#VAR_023663; OMIM: 174763.0021; dbSNP: rs121918056

NCBI 1000 Genomes Browser:

rs121918056

Molecular consequence:

NM_001126131.2:c.679C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.679C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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
SCV003739502	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 27, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12707443, 15349879, 25281868, 28471437 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003739502

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 27, 2021)

germline

clinical testing

PubMed (4)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).

Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M.

Neurology. 2003 Apr 22;60(8):1354-6.

PubMed [citation]

PMID:: 12707443

Sequence analysis of familial PEO shows additional mutations associated with the 752C-->T and 3527C-->T changes in the POLG1 gene.

Lamantea E, Zeviani M.

Ann Neurol. 2004 Sep;56(3):454-5. No abstract available.

PubMed [citation]

PMID:: 15349879

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003739502.2

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

Description

The c.679C>T (p.R227W) alteration is located in exon 3 (coding exon 2) of the POLG gene. This alteration results from a C to T substitution at nucleotide position 679, causing the arginine (R) at amino acid position 227 to be replaced by a tryptophan (W). Based on data from the Genome Aggregation Database (gnomAD) database, the POLG c.679C>T alteration was observed in 0.0004% (1/247,648) of total alleles studied, with a frequency of 0.003% (1/30,600) in the South Asian subpopulation. This alteration has been previously reported in multiple patients with autosomal recessive POLG-related mitochondrial disorders (Agostino 2003; Lamantea, 2004; de Vries, 2007; Horga, 2014; Hikmat, 2017). This amino acid position is highly conserved in available vertebrate species. The p.R227W alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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

ClinVar

Relating variation to medicine