NM_002693.3(POLG):c.3646G>A (p.Glu1216Lys) AND Progressive sclerosing poliodystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 16, 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:: RCV003626303.2

Allele description [Variation Report for NM_002693.3(POLG):c.3646G>A (p.Glu1216Lys)]

NM_002693.3(POLG):c.3646G>A (p.Glu1216Lys)

Genes:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
FANCI:FA complementation group I [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.3646G>A (p.Glu1216Lys)

HGVS:

NC_000015.10:g.89316825C>T
NG_008218.2:g.22971G>A
NG_011736.1:g.77863C>T
NM_001113378.2:c.*366C>TMANE SELECT
NM_001126131.2:c.3646G>A
NM_001376910.1:c.*366C>T
NM_001376911.1:c.*366C>T
NM_002693.3:c.3646G>AMANE SELECT
NM_018193.3:c.*366C>T
NP_001119603.1:p.Glu1216Lys
NP_002684.1:p.Glu1216Lys
NP_002684.1:p.Glu1216Lys
LRG_500t1:c.*366C>T
LRG_765t1:c.3646G>A
LRG_500:g.77863C>T
LRG_765:g.22971G>A
LRG_765p1:p.Glu1216Lys
NC_000015.9:g.89860056C>T
NM_001113378.1:c.*366C>T
NM_002693.2:c.3646G>A

Protein change:

E1216K

Molecular consequence:

NM_001113378.2:c.*366C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001376910.1:c.*366C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001376911.1:c.*366C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_018193.3:c.*366C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126131.2:c.3646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.3646G>A - 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

Recent activity

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Staphylococcal Infections
Staphylococcal Infections
Infections with bacteria of the genus STAPHYLOCOCCUS.<br/>Year introduced: STAPHYLOCOCCAL INFECTIONS, GASTROINTESTINAL & STAPHYLOCOCCAL INFECTIONS, RESPIRATORY were headings 1963-1967

MeSH
CYP714A2 cytochrome P450, family 714, subfamily A, polypeptide 2 [Arabidopsis th...
CYP714A2 cytochrome P450, family 714, subfamily A, polypeptide 2 [Arabidopsis thaliana]
Gene ID:832559

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004467548	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 16, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004467548

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 16, 2023)

germline

clinical testing

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004467548.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1216 of the POLG protein (p.Glu1216Lys). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive.

#	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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