NM_002693.3(POLG):c.3131T>C (p.Val1044Ala) AND Progressive sclerosing poliodystrophy

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 30, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000234341.21

Allele description [Variation Report for NM_002693.3(POLG):c.3131T>C (p.Val1044Ala)]

NM_002693.3(POLG):c.3131T>C (p.Val1044Ala)

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.3131T>C (p.Val1044Ala)

HGVS:

NC_000015.10:g.89319073A>G
NG_008218.2:g.20723T>C
NG_011736.1:g.80111A>G
NM_001126131.2:c.3131T>C
NM_002693.3:c.3131T>CMANE SELECT
NP_001119603.1:p.Val1044Ala
NP_002684.1:p.Val1044Ala
NP_002684.1:p.Val1044Ala
LRG_765t1:c.3131T>C
LRG_500:g.80111A>G
LRG_765:g.20723T>C
LRG_765p1:p.Val1044Ala
NC_000015.9:g.89862304A>G
NM_001126131.1:c.3131T>C
NM_002693.2:c.3131T>C
NM_002693.3:c.3131T>C
p.V1044A

Protein change:

V1044A

Links:

dbSNP: rs150233690

NCBI 1000 Genomes Browser:

rs150233690

Molecular consequence:

NM_001126131.2:c.3131T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.3131T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000287671	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000887299	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 1, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21357833, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000287671

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 30, 2024)

germline

clinical testing

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

SCV000887299

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 1, 2018)

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

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

POLG1 manifestations in childhood.

Isohanni P, Hakonen AH, Euro L, Paetau I, Linnankivi T, Liukkonen E, Wallden T, Luostarinen L, Valanne L, Paetau A, Uusimaa J, Lönnqvist T, Suomalainen A, Pihko H.

Neurology. 2011 Mar 1;76(9):811-5. doi: 10.1212/WNL.0b013e31820e7b25.

PubMed [citation]

PMID:: 21357833

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000287671.11

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

#	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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000887299.1

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

Description

The NM_002693.2:c.3131T>C (NP_002684.1:p.Val1044Ala) [GRCH38: NC_000015.10:g.89319073A>G] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:21357833 . This variant meets the following evidence codes reported in the ACMG-guideline. PP3:Computational evidence/predictors indicate the variant has deleterious effect on POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.

#	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: Nov 24, 2024

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