NM_002693.3(POLG):c.1399G>A (p.Ala467Thr) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 26, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000184011.10

Allele description [Variation Report for NM_002693.3(POLG):c.1399G>A (p.Ala467Thr)]

NM_002693.3(POLG):c.1399G>A (p.Ala467Thr)

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.1399G>A (p.Ala467Thr)

Other names:

p.A467T:GCC>ACC

HGVS:

NC_000015.10:g.89327201C>T
NG_008218.2:g.12595G>A
NM_001126131.2:c.1399G>A
NM_002693.3:c.1399G>AMANE SELECT
NP_001119603.1:p.Ala467Thr
NP_002684.1:p.Ala467Thr
NP_002684.1:p.Ala467Thr
LRG_765t1:c.1399G>A
LRG_765:g.12595G>A
LRG_765p1:p.Ala467Thr
NC_000015.9:g.89870432C>T
NM_001126131.1:c.1399G>A
NM_002693.2:c.1399G>A
NM_002693.3:c.1399G>A
P54098:p.Ala467Thr
p.A467T

Protein change:

A467T; ALA467THR

Links:

UniProtKB: P54098#VAR_012155; OMIM: 174763.0002; dbSNP: rs113994095

NCBI 1000 Genomes Browser:

rs113994095

Molecular consequence:

NM_001126131.2:c.1399G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.1399G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 (PEOA1)
Synonyms:: PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL DOMINANT 1
Identifiers:: MONDO: MONDO:0024528; MedGen: C1834846; OMIM: 157640

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000236534	Courtagen Diagnostics Laboratory, Courtagen Life Sciences	criteria provided, single submitter (Courtagen Life Sciences Classifications)	Pathogenic (Dec 16, 2013)	maternal	clinical testing	Citation Link,
SCV001522833	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 26, 2020)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19578034, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000236534

Courtagen Diagnostics Laboratory, Courtagen Life Sciences

criteria provided, single submitter

(Courtagen Life Sciences Classifications)

Pathogenic
(Dec 16, 2013)

maternal

clinical testing

Citation Link,

SCV001522833

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 26, 2020)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The unfolding clinical spectrum of POLG mutations.

Blok MJ, van den Bosch BJ, Jongen E, Hendrickx A, de Die-Smulders CE, Hoogendijk JE, Brusse E, de Visser M, Poll-The BT, Bierau J, de Coo IF, Smeets HJ.

J Med Genet. 2009 Nov;46(11):776-85. doi: 10.1136/jmg.2009.067686. Epub 2009 Jul 2.

PubMed [citation]

PMID:: 19578034

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 Courtagen Diagnostics Laboratory, Courtagen Life Sciences, SCV000236534.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV001522833.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. Both variants have been previously reported as disease-causing [PMID 19578034 etc.]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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