NM_002693.2(POLG):c.3559C>T (p.Arg1187Trp) AND Progressive sclerosing poliodystrophy

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Uncertain significance(1) (Last evaluated: Dec 31, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000633564.3

Allele description [Variation Report for NM_002693.2(POLG):c.3559C>T (p.Arg1187Trp)]

NM_002693.2(POLG):c.3559C>T (p.Arg1187Trp)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.3559C>T (p.Arg1187Trp)
Other names:
p.R1187W:CGG>TGG
HGVS:
  • NC_000015.10:g.89317460G>A
  • NG_008218.2:g.22336C>T
  • NG_011736.1:g.78498G>A
  • NM_001126131.2:c.3559C>T
  • NM_002693.2:c.3559C>T
  • NP_001119603.1:p.Arg1187Trp
  • NP_002684.1:p.Arg1187Trp
  • LRG_765t1:c.3559C>T
  • LRG_500:g.78498G>A
  • LRG_765:g.22336C>T
  • LRG_765p1:p.Arg1187Trp
  • NC_000015.9:g.89860691G>A
Protein change:
R1187W
Links:
dbSNP: rs369544574
NCBI 1000 Genomes Browser:
rs369544574
Molecular consequence:
  • NM_001126131.2:c.3559C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.2:c.3559C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000754810Invitaecriteria provided, single submitter
Benign
(Dec 31, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000887302Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Uncertain significance
(Oct 1, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency.

Reichenbach J, Schubert R, Horvàth R, Petersen J, Fütterer N, Malle E, Stumpf A, Gebhardt BR, Koehl U, Schraven B, Zielen S.

Pediatr Res. 2006 Sep;60(3):321-6. Epub 2006 Jul 20.

PubMed [citation]
PMID:
16857757
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000754810.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000887302.1

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

Description

The NM_002693.2:c.3559C>T (NP_002684.1:p.Arg1187Trp) [GRCH38: NC_000015.10:g.89317460G>A] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:16857757 . This variant meets the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PP2:This is a missense variant in POLG with a low rate of benign and high rate of pathogenic missense variations. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Likely Pathogenic.

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

Last Updated: Jul 10, 2021

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