NM_002693.3(POLG):c.1491G>C (p.Gln497His) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 7, 2024
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:: RCV000676325.15

Allele description [Variation Report for NM_002693.3(POLG):c.1491G>C (p.Gln497His)]

NM_002693.3(POLG):c.1491G>C (p.Gln497His)

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.1491G>C (p.Gln497His)

Other names:

p.Q497H:CAG>CAC

HGVS:

NC_000015.10:g.89327006C>G
NG_008218.2:g.12790G>C
NM_001126131.2:c.1491G>C
NM_002693.3:c.1491G>CMANE SELECT
NP_001119603.1:p.Gln497His
NP_002684.1:p.Gln497His
NP_002684.1:p.Gln497His
LRG_765t1:c.1491G>C
LRG_765:g.12790G>C
LRG_765p1:p.Gln497His
NC_000015.9:g.89870237C>G
NM_001126131.1:c.1491G>C
NM_002693.2:c.1491G>C
P54098:p.Gln497His

Protein change:

Q497H; GLN497HIS

Links:

UniProtKB: P54098#VAR_023669; OMIM: 174763.0016; dbSNP: rs121918052

NCBI 1000 Genomes Browser:

rs121918052

Molecular consequence:

NM_001126131.2:c.1491G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.1491G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000242283	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 7, 2024)	germline	clinical testing	Citation Link,
SCV000802091	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Uncertain significance (Mar 8, 2016)	unknown	clinical testing
SCV002501870	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 5, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15824347, 18991199, 25025039, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000242283

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 7, 2024)

germline

clinical testing

Citation Link,

SCV000802091

Mayo Clinic Laboratories, Mayo Clinic

no assertion criteria provided

Uncertain significance
(Mar 8, 2016)

unknown

clinical testing

SCV002501870

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 5, 2021)

germline

clinical testing

PubMed (4)
[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	1	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

Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations.

Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM, Engelsen BA, Moen G, Bindoff LA.

Neurology. 2005 Apr 12;64(7):1204-8.

PubMed [citation]

PMID:: 15824347

Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI.

Brunetti-Pierri N, Selby K, O'Sullivan M, Hendson G, Truong C, Waters PJ, Wong LJ.

Neuropediatrics. 2008 Jun;39(3):179-83. doi: 10.1055/s-0028-1093334. Epub 2008 Nov 7.

PubMed [citation]

PMID:: 18991199

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000242283.13

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18991199, 18546365, 25025039, 15824347, 19813183, 17088268, 25065347, 16545482, 21357833, 22729384, 25476511, 33726816, 26942291, 28480171, 32949115, 32183364, 38434220, 16080118)

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV000802091.1

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

#	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

From AiLife Diagnostics, AiLife Diagnostics, SCV002501870.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

#	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		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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