NM_002693.3(POLG):c.328C>T (p.His110Tyr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 2021
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:: RCV001804925.8

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)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002051277	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 20, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33469851, 27826120, 20185557, 18546365 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002051277

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 20, 2021)

germline

clinical testing

PubMed (4)
[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

Clinico-pathological and Molecular Spectrum of Mitochondrial Polymerase γ Mutations in a Cohort from India.

Deepha S, Govindaraj P, Sankaran BP, Chiplunkar S, Kashinkunti C, Nunia V, Nagappa M, Sinha S, Khanna T, Thangaraj K, Taly AB, Gayathri N.

J Mol Neurosci. 2021 Nov;71(11):2219-2228. doi: 10.1007/s12031-020-01765-8. Epub 2021 Jan 19.

PubMed [citation]

PMID:: 33469851

Mitochondrial oxidative phosphorylation disorders in children: Phenotypic, genotypic and biochemical correlations in 85 patients from South India.

Sonam K, Bindu PS, Srinivas Bharath MM, Govindaraj P, Gayathri N, Arvinda HR, Chiplunkar S, Nagappa M, Sinha S, Khan NA, Nunia V, Paramasivam A, Thangaraj K, Taly AB.

Mitochondrion. 2017 Jan;32:42-49. doi: 10.1016/j.mito.2016.11.002. Epub 2016 Nov 5.

PubMed [citation]

PMID:: 27826120

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002051277.1

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

Description

Variant summary: POLG c.328C>T (p.His110Tyr) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 238934 control chromosomes (gnomAD). c.328C>T has been reported in the literature in individuals affected with features of Alpers syndrome, chronic progressive external ophthalmoplegia and sensory ataxic neuropathy with cerebellar syndrome (Wong_2008, Sonam_2017, Deepha_2021). These reports do not provide unequivocal conclusions about association of the variant with POLG-Related Spectrum Disorders. Experimental evidence evaluating an impact on protein function in yeast assays, demonstrated the variant to function similarly to wild-type (Stumpf_2010). Seven ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and one ClinVar submitter (evaluation after 2014) cites it as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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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