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NM_002693.3(POLG):c.3523C>T (p.Gln1175Ter) AND Progressive sclerosing poliodystrophy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 23, 2017
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:
RCV000686623.2

Allele description

NM_002693.3(POLG):c.3523C>T (p.Gln1175Ter)

Genes:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.3(POLG):c.3523C>T (p.Gln1175Ter)
Other names:
NM_002693.2(POLG):c.3523C>T; p.Gln1175Ter
HGVS:
  • NC_000015.10:g.89317496G>A
  • NG_008218.2:g.22300C>T
  • NG_011736.1:g.78534G>A
  • NM_001126131.2:c.3523C>T
  • NM_002693.3:c.3523C>TMANE SELECT
  • NP_001119603.1:p.Gln1175Ter
  • NP_002684.1:p.Gln1175Ter
  • NP_002684.1:p.Gln1175Ter
  • LRG_765t1:c.3523C>T
  • LRG_500:g.78534G>A
  • LRG_765:g.22300C>T
  • LRG_765p1:p.Gln1175Ter
  • NC_000015.9:g.89860727G>A
  • NC_000015.9:g.89860727G>A
  • NM_002693.2:c.3523C>T
Protein change:
Q1175*
Links:
dbSNP: rs1567184117
NCBI 1000 Genomes Browser:
rs1567184117
Molecular consequence:
  • NM_001126131.2:c.3523C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_002693.3:c.3523C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Progressive sclerosing poliodystrophy (MTDPS4A)
Synonyms:
Alpers disease; Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis; Alpers progressive infantile poliodystrophy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008758; MedGen: C0205710; Orphanet: 726; OMIM: 203700

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000814149Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 23, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.

Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC.

Hum Mutat. 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824.

PubMed [citation]
PMID:
18546365
PMCID:
PMC2891192

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000814149.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln1175*) in the POLG gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a POLG-related disease. Loss-of-function variants in POLG are known to be pathogenic (PMID: 18546365). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Dec 9, 2023