NM_002693.3(POLG):c.3570del (p.Lys1191fs) AND Progressive sclerosing poliodystrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 19, 2022
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:: RCV002847998.2

Allele description

NM_002693.3(POLG):c.3570del (p.Lys1191fs)

Genes:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.3570del (p.Lys1191fs)

HGVS:

NC_000015.10:g.89317450del
NG_008218.2:g.22347del
NG_011736.1:g.78488del
NM_001126131.2:c.3570del
NM_002693.3:c.3570delMANE SELECT
NP_001119603.1:p.Lys1191fs
NP_002684.1:p.Lys1191Argfs
NP_002684.1:p.Lys1191fs
LRG_765t1:c.3569del
LRG_500:g.78488del
LRG_765:g.22347del
LRG_765p1:p.Lys1191Argfs
NC_000015.9:g.89860680del
NC_000015.9:g.89860681del
NM_002693.2:c.3569delG

Protein change:

K1191fs

Molecular consequence:

NM_001126131.2:c.3570del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002693.3:c.3570del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003226481	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 19, 2022)	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

SCV003226481

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 19, 2022)

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 Invitae, SCV003226481.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys1191Argfs*3) 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).

#	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: May 12, 2024

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