NM_002693.3(POLG):c.1889A>G (p.Asn630Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 6, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000188669.3

Allele description [Variation Report for NM_002693.3(POLG):c.1889A>G (p.Asn630Ser)]

NM_002693.3(POLG):c.1889A>G (p.Asn630Ser)

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.1889A>G (p.Asn630Ser)

Other names:

p.N630S:AAC>AGC

HGVS:

NC_000015.10:g.89325510T>C
NG_008218.2:g.14286A>G
NM_001126131.2:c.1889A>G
NM_002693.3:c.1889A>GMANE SELECT
NP_001119603.1:p.Asn630Ser
NP_002684.1:p.Asn630Ser
NP_002684.1:p.Asn630Ser
LRG_765t1:c.1889A>G
LRG_765:g.14286A>G
LRG_765p1:p.Asn630Ser
NC_000015.9:g.89868741T>C
NM_002693.2:c.1889A>G

Protein change:

N630S

Links:

dbSNP: rs796052905

NCBI 1000 Genomes Browser:

rs796052905

Molecular consequence:

NM_001126131.2:c.1889A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.1889A>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
SCV000242293	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jun 16, 2014)	germline	clinical testing	Citation Link,
SCV001879830	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Uncertain significance (Oct 6, 2020)	unknown	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

SCV000242293

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jun 16, 2014)

germline

clinical testing

Citation Link,

SCV001879830

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics criteria)

Uncertain significance
(Oct 6, 2020)

unknown

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	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

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, SCV000242293.10

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

Description

p.Asn630Ser (AAC>AGC): c.1889 A>G in exon 10 of the POLG gene (NM_002693.2). The N630S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N630S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved in mammals, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, multiple missense mutations in nearby residues have been reported in association with POLG-related disorders, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

#	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, SCV001879830.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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