U.S. flag

An official website of the United States government

NM_002693.3(POLG):c.386C>T (p.Pro129Leu) AND Progressive sclerosing poliodystrophy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 14, 2023
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:
RCV003448815.2

Allele description [Variation Report for NM_002693.3(POLG):c.386C>T (p.Pro129Leu)]

NM_002693.3(POLG):c.386C>T (p.Pro129Leu)

Genes:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.3(POLG):c.386C>T (p.Pro129Leu)
HGVS:
  • NC_000015.10:g.89333369G>A
  • NG_008218.2:g.6427C>T
  • NM_001126131.2:c.386C>T
  • NM_001406557.1:c.441C>T
  • NM_002693.3:c.386C>TMANE SELECT
  • NP_001119603.1:p.Pro129Leu
  • NP_001393486.1:p.Ala147=
  • NP_002684.1:p.Pro129Leu
  • NP_002684.1:p.Pro129Leu
  • LRG_765t1:c.386C>T
  • LRG_765:g.6427C>T
  • LRG_765p1:p.Pro129Leu
  • NC_000015.9:g.89876600G>A
  • NM_002693.2:c.386C>T
Protein change:
P129L
Molecular consequence:
  • NM_001126131.2:c.386C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.386C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406557.1:c.441C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004176568Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 14, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004176568.1

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

Description

The missense c.386C>T(p.Pro129Leu) variant in POLG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Pro129Leu variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has not been reported to the ClinVar database. The amino acid change p.Pro129Leu in POLG is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 129 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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

Last Updated: Apr 6, 2024