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NM_002693.3(POLG):c.3131T>C (p.Val1044Ala) AND POLG-Related Spectrum Disorders

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 15, 2018
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:
RCV000778452.12

Allele description [Variation Report for NM_002693.3(POLG):c.3131T>C (p.Val1044Ala)]

NM_002693.3(POLG):c.3131T>C (p.Val1044Ala)

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.3131T>C (p.Val1044Ala)
HGVS:
  • NC_000015.10:g.89319073A>G
  • NG_008218.2:g.20723T>C
  • NG_011736.1:g.80111A>G
  • NM_001126131.2:c.3131T>C
  • NM_002693.3:c.3131T>CMANE SELECT
  • NP_001119603.1:p.Val1044Ala
  • NP_002684.1:p.Val1044Ala
  • NP_002684.1:p.Val1044Ala
  • LRG_765t1:c.3131T>C
  • LRG_500:g.80111A>G
  • LRG_765:g.20723T>C
  • LRG_765p1:p.Val1044Ala
  • NC_000015.9:g.89862304A>G
  • NM_001126131.1:c.3131T>C
  • NM_002693.2:c.3131T>C
  • NM_002693.3:c.3131T>C
  • p.V1044A
Protein change:
V1044A
Links:
dbSNP: rs150233690
NCBI 1000 Genomes Browser:
rs150233690
Molecular consequence:
  • NM_001126131.2:c.3131T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.3131T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000914700Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Uncertain significance
(Nov 15, 2018) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum.

Tang S, Wang J, Lee NC, Milone M, Halberg MC, Schmitt ES, Craigen WJ, Zhang W, Wong LJ.

J Med Genet. 2011 Oct;48(10):669-81. doi: 10.1136/jmedgenet-2011-100222. Epub 2011 Aug 31.

PubMed [citation]
PMID:
21880868

Diagnosis of monogenic liver diseases in childhood by next-generation sequencing.

Stalke A, Skawran B, Auber B, Illig T, Schlegelberger B, Junge N, Goldschmidt I, Leiskau C, von Neuhoff N, Baumann U, Pfister ED.

Clin Genet. 2018 Mar;93(3):665-670. doi: 10.1111/cge.13120. Epub 2017 Dec 12.

PubMed [citation]
PMID:
28776642
See all PubMed Citations (4)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914700.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The POLG c.3131T>C (p.Val1044Ala) has been reported in four studies and in a total of five patients including one in a compound heterozygous state, and four in a heterozygous state (Isohanni et al. 2011; Tang et al. 2011; Stalke et al. 2018; Traboulsee et al. 2017). Two of the individuals identified with the variant have multiple sclerosis, two have mitochondrial disease, and the fifth was noted to have POLG-deficiency (Isohanni et al. 2011; Tang et al. 2011; Stalke et al. 2018; Traboulsee et al. 2017). The p.Val1044Ala variant was found in one control out of 1200 control individuals and is reported at a frequency of 0.003319 in the Other population of the Exome Aggregation Consortium. Based on the evidence, the p.Val1044Ala is classified as a variant of unknown significance, but suspicious for pathogenicity for POLG-related spectrum disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024