NM_002693.3(POLG):c.739dup (p.Leu247fs) AND Progressive sclerosing poliodystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 2, 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:: RCV003627020.2

Allele description [Variation Report for NM_002693.3(POLG):c.739dup (p.Leu247fs)]

NM_002693.3(POLG):c.739dup (p.Leu247fs)

Gene:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.739dup (p.Leu247fs)

HGVS:

NC_000015.10:g.89330201dup
NG_008218.2:g.9599dup
NM_001126131.2:c.739dup
NM_002693.3:c.739dupMANE SELECT
NP_001119603.1:p.Leu247fs
NP_002684.1:p.Leu247Profs
NP_002684.1:p.Leu247fs
LRG_765t1:c.735dup
LRG_765:g.9599dup
LRG_765p1:p.Leu247Profs
NC_000015.9:g.89873427_89873428insG
NC_000015.9:g.89873432dup
NM_002693.2:c.735dup

Protein change:

L247fs

Molecular consequence:

NM_001126131.2:c.739dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002693.3:c.739dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Mus musculus elongation factor RNA polymerase II-like 3 (Ell3), mRNA
Mus musculus elongation factor RNA polymerase II-like 3 (Ell3), mRNA
gi|35901197|ref|NM_145973.2|

Nucleotide
Homo sapiens ubiquitin specific peptidase 17 like family member 22 (USP17L22), m...
Homo sapiens ubiquitin specific peptidase 17 like family member 22 (USP17L22), mRNA
gi|379030609|ref|NM_001256863.1|

Nucleotide
uncharacterized protein LOC18782137 [Prunus persica]
uncharacterized protein LOC18782137 [Prunus persica]
gi|595967184|ref|XP_007217258.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004382828	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18546365, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004382828

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 2, 2023)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004382828.1

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

Description

This sequence change creates a premature translational stop signal (p.Leu247Profs*28) in the POLG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLG are known to be pathogenic (PMID: 18546365). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLG-related conditions. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024

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