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NM_002693.2(POLG):c.3383G>A (p.Arg1128His)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Aug 20, 2021)
Last evaluated:
Oct 3, 2020
Accession:
VCV000593423.3
Variation ID:
593423
Description:
single nucleotide variant
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NM_002693.2(POLG):c.3383G>A (p.Arg1128His)

Allele ID
584487
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q26.1
Genomic location
15: 89318640 (GRCh38) GRCh38 UCSC
15: 89861871 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.89318640C>T
NC_000015.9:g.89861871C>T
NM_001126131.2:c.3383G>A NP_001119603.1:p.Arg1128His missense
... more HGVS
Protein change
R1128H
Other names
-
Canonical SPDI
NC_000015.10:89318639:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
dbSNP: rs1405268319
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, single submitter Aug 1, 2017 RCV000728455.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Oct 3, 2020 RCV000758473.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
POLG - - GRCh38
GRCh37
1276 1392

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 01, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000856033.1
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Oct 01, 2018)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV000887186.1
Submitted: (Nov 16, 2018)
Evidence details
Comment:
The NM_002693.2:c.3383G>A (NP_002684.1:p.Arg1128His) [GRCH38: NC_000015.10:g.89318640C>T] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets … (more)
Uncertain significance
(Oct 03, 2020)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Invitae
Accession: SCV001545289.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces arginine with histidine at codon 1128 of the POLG protein (p.Arg1128His). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799655.1
Submitted: (Aug 19, 2021)
Evidence details
Uncertain significance
(Jun 16, 2020)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001804495.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Reported previously in a one year old male with developmental delay, liver disease, and microcephaly who had another missense variant on the opposite allele (Wong … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Wong LJ Human mutation 2008 PMID: 18546365
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=POLG - - - -

Text-mined citations for rs1405268319...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021