NM_002693.3(POLG):c.3294T>G (p.Asn1098Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 3, 2022
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:: RCV002273670.5

Allele description [Variation Report for NM_002693.3(POLG):c.3294T>G (p.Asn1098Lys)]

NM_002693.3(POLG):c.3294T>G (p.Asn1098Lys)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.3294T>G (p.Asn1098Lys)

HGVS:

NC_000015.10:g.89318729A>C
NG_008218.2:g.21067T>G
NG_011736.1:g.79767A>C
NM_001126131.2:c.3294T>G
NM_002693.3:c.3294T>GMANE SELECT
NP_001119603.1:p.Asn1098Lys
NP_002684.1:p.Asn1098Lys
LRG_765t1:c.3294T>G
LRG_500:g.79767A>C
LRG_765:g.21067T>G
NC_000015.9:g.89861960A>C
NM_002693.2:c.3294T>G

Protein change:

N1098K

Links:

dbSNP: rs374224714

NCBI 1000 Genomes Browser:

rs374224714

Molecular consequence:

NM_001126131.2:c.3294T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.3294T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002558562	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 21, 2022)	germline	clinical testing	Citation Link,
SCV002770710	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Feb 3, 2022)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33486010, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002558562

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 21, 2022)

germline

clinical testing

Citation Link,

SCV002770710

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Feb 3, 2022)

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes.

Bychkov IO, Itkis YS, Tsygankova PG, Krylova TD, Mikhaylova SV, Klyushnikov SA, Pechatnikova NL, Degtyareva AV, Nikolaeva EA, Seliverstov YA, Kurbatov SA, Dadali EL, Rudenskaya GE, Illarioshkin SN, Zakharova EY.

Mitochondrion. 2021 Mar;57:205-212. doi: 10.1016/j.mito.2021.01.004. Epub 2021 Jan 21.

PubMed [citation]

PMID:: 33486010

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV002558562.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33486010)

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

From Athena Diagnostics, SCV002770710.1

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

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

Last Updated: May 7, 2024

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