NM_002693.2(POLG):c.3176A>G (p.Asn1059Ser) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 4, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000188605.4

Allele description [Variation Report for NM_002693.2(POLG):c.3176A>G (p.Asn1059Ser)]

NM_002693.2(POLG):c.3176A>G (p.Asn1059Ser)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.3176A>G (p.Asn1059Ser)
Other names:
p.N1059S:AAT>AGT
HGVS:
  • NC_000015.10:g.89319028T>C
  • NG_008218.2:g.20768A>G
  • NM_002693.2:c.3176A>G
  • NP_002684.1:p.Asn1059Ser
  • LRG_765t1:c.3176A>G
  • LRG_765:g.20768A>G
  • LRG_765p1:p.Asn1059Ser
  • NC_000015.9:g.89862259T>C
Protein change:
N1059S
Links:
dbSNP: rs201192905
NCBI 1000 Genomes Browser:
rs201192905
Molecular consequence:
  • NM_002693.2:c.3176A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000242228GeneDxcriteria provided, single submitter
Uncertain significance
(Oct 11, 2016)
germlineclinical testing

Citation Link,

SCV000614721Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(May 4, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Need AC, McEvoy JP, Gennarelli M, Heinzen EL, Ge D, Maia JM, Shianna KV, He M, Cirulli ET, Gumbs CE, Zhao Q, Campbell CR, Hong L, Rosenquist P, Putkonen A, Hallikainen T, Repo-Tiihonen E, Tiihonen J, Levy DL, Meltzer HY, Goldstein DB.

Am J Hum Genet. 2012 Aug 10;91(2):303-12. doi: 10.1016/j.ajhg.2012.06.018. Epub 2012 Aug 2.

PubMed [citation]
PMID:
22863191
PMCID:
PMC3415532

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, SCV000242228.9

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

Description

A variant of uncertain significance has been identified in the POLG gene. The N1059S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N1059S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. 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. However, the N1059S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

From Athena Diagnostics Inc, SCV000614721.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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