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NM_002693.3(POLG):c.3347T>C (p.Met1116Thr) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Dec 30, 2021
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:
RCV000188619.28

Allele description [Variation Report for NM_002693.3(POLG):c.3347T>C (p.Met1116Thr)]

NM_002693.3(POLG):c.3347T>C (p.Met1116Thr)

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.3347T>C (p.Met1116Thr)
Other names:
p.M1116T:ATG>ACG; p.Met1116Thr
HGVS:
  • NC_000015.10:g.89318676A>G
  • NG_008218.2:g.21120T>C
  • NG_011736.1:g.79714A>G
  • NM_001126131.2:c.3347T>C
  • NM_002693.3:c.3347T>CMANE SELECT
  • NP_001119603.1:p.Met1116Thr
  • NP_002684.1:p.Met1116Thr
  • NP_002684.1:p.Met1116Thr
  • LRG_765t1:c.3347T>C
  • LRG_500:g.79714A>G
  • LRG_765:g.21120T>C
  • LRG_765p1:p.Met1116Thr
  • NC_000015.9:g.89861907A>G
  • NM_002693.2:c.3347T>C
Protein change:
M1116T
Links:
dbSNP: rs764036283
NCBI 1000 Genomes Browser:
rs764036283
Molecular consequence:
  • NM_001126131.2:c.3347T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.3347T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000242242GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(May 22, 2014) 		germlineclinical testing

Citation Link,

SCV001961530CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)		Uncertain significance
(Aug 1, 2021) 		germlineclinical testing

Citation Link,

SCV002541292Mayo Clinic Laboratories, Mayo Clinic
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 30, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From GeneDx, SCV000242242.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

p.Met1116Thr (ATG>ACG): c.3347 T>C in exon 21 of the POLG gene (NM_002693.2). The M1116T 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 M1116T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (V1106I, H1110Y, L1113P) have been reported in association with POLG-related disorders, supporting the functional importance of this region of the protein. However, 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 INFANT-EPI panel(s).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From CeGaT Center for Human Genetics Tuebingen, SCV001961530.20

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV002541292.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024