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NM_002693.2(POLG):c.3640C>T (p.Gln1214Ter)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jul 16, 2021)
Last evaluated:
Jun 30, 2020
Accession:
VCV000488798.5
Variation ID:
488798
Description:
single nucleotide variant
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NM_002693.2(POLG):c.3640C>T (p.Gln1214Ter)

Allele ID
482080
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q26.1
Genomic location
15: 89317379 (GRCh38) GRCh38 UCSC
15: 89860610 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.89317379G>A
NC_000015.9:g.89860610G>A
NG_008218.2:g.22417C>T
... more HGVS
Protein change
Q1214*
Other names
-
Canonical SPDI
NC_000015.10:89317378:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA7724076
dbSNP: rs781256643
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Jun 30, 2020 RCV000579250.3
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 28, 2020 RCV000758431.2
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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
1310 1429

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jun 28, 2020)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Invitae
Accession: SCV001506455.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change results in a premature translational stop signal in the POLG gene (p.Gln1214*). While this is not anticipated to result in nonsense mediated … (more)
Uncertain significance
(Jun 30, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000680672.3
Submitted: (Jul 16, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation as the last … (more)
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: SCV000887135.1
Submitted: (Nov 16, 2018)
Evidence details
Comment:
The NM_002693.2:c.3640C>T (NP_002684.1:p.Gln1214Ter) [GRCH38: NC_000015.10:g.89317379G>A] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the … (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
Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. Tang S Journal of medical genetics 2011 PMID: 21880868

Text-mined citations for rs781256643...

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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 Sep 23, 2021