NM_002693.2(POLG):c.3488_3491dup (p.Ala1165Valfs) AND Progressive sclerosing poliodystrophy

Clinical significance:Pathogenic (Last evaluated: Oct 1, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_002693.2(POLG):c.3488_3491dup (p.Ala1165Valfs)]

NM_002693.2(POLG):c.3488_3491dup (p.Ala1165Valfs)

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_002693.2(POLG):c.3488_3491dup (p.Ala1165Valfs)
  • NC_000015.10:g.89317528_89317531dup
  • NG_008218.2:g.22265_22268dup
  • NM_002693.2:c.3488_3491dup
  • NP_002684.1:p.Ala1165Valfs
  • LRG_765t1:c.3488_3491dup
  • LRG_765:g.22265_22268dup
  • LRG_765p1:p.Ala1165Valfs
  • NC_000015.9:g.89860757_89860760dup
  • NM_002693.2:c.3490_3493dup


Progressive sclerosing poliodystrophy (MTDPS4A)
Alpers Syndrome; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers-Huttenlocher Syndrome
MedGen: C0205710; Orphanet: 726; OMIM: 203700

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000887134Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicinecriteria provided, single submitter
(Oct 1, 2018)
germlineclinical testing

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

Summary from all submissions

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



Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicine, SCV000887134.1

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


The NM_002693.2:c.3490_3493dup (NP_002684.1:p.Ala1165ValfsTer9) [GRCH38: NC_000015.10:g.89317528_89317531dup] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predicted null variant in POLG where loss of function is a known mechanism of disease. 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. PM4:This variant causes alteration in the length of expressed protein. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. 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 Pathogenic.

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

Last Updated: Jun 17, 2019

Support Center