NM_002693.3(POLG):c.328C>T (p.His110Tyr) AND Inborn genetic diseases

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 4, 2019
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:: RCV002317148.9

Allele description [Variation Report for NM_002693.3(POLG):c.328C>T (p.His110Tyr)]

NM_002693.3(POLG):c.328C>T (p.His110Tyr)

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.328C>T (p.His110Tyr)

Other names:

p.H110Y:CAC>TAC

HGVS:

NC_000015.10:g.89333427G>A
NG_008218.2:g.6369C>T
NM_001126131.2:c.328C>T
NM_002693.3:c.328C>TMANE SELECT
NP_001119603.1:p.His110Tyr
NP_002684.1:p.His110Tyr
NP_002684.1:p.His110Tyr
LRG_765t1:c.328C>T
LRG_765:g.6369C>T
LRG_765p1:p.His110Tyr
NC_000015.9:g.89876658G>A
NM_002693.2:c.328C>T
p.His110Tyr

Protein change:

H110Y

Links:

dbSNP: rs139599587

NCBI 1000 Genomes Browser:

rs139599587

Molecular consequence:

NM_001126131.2:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002693.3:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000850916	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 4, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18546365, 20185557, 27826120 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000850916

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 4, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.

Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC.

Hum Mutat. 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824.

PubMed [citation]

PMID:: 18546365
PMCID:: PMC2891192

mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae.

Stumpf JD, Bailey CM, Spell D, Stillwagon M, Anderson KS, Copeland WC.

Hum Mol Genet. 2010 Jun 1;19(11):2123-33. doi: 10.1093/hmg/ddq089. Epub 2010 Feb 25.

PubMed [citation]

PMID:: 20185557
PMCID:: PMC2865372

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000850916.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.H110Y variant (also known as c.328C>T), located in coding exon 1 of the POLG gene, results from a C to T substitution at nucleotide position 328. The histidine at codon 110 is replaced by tyrosine, an amino acid with similar properties. This alteration has been reported in a three year old patient with some features of Alpers syndrome and in an eleven year old girl with CPEO plus syndrome (Wong LJ et al. Hum. Mutat., 2008 Sep;29:E150-72; Sonam K et al. Mitochondrion, 2017 Jan;32:42-49). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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