NM_198253.3(TERT):c.2594G>A (p.Arg865His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 18, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_198253.3(TERT):c.2594G>A (p.Arg865His)]

NM_198253.3(TERT):c.2594G>A (p.Arg865His)

TERT:telomerase reverse transcriptase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_198253.3(TERT):c.2594G>A (p.Arg865His)
  • NC_000005.10:g.1266524C>T
  • NG_009265.1:g.33524G>A
  • NM_001193376.2:c.2594G>A
  • NM_198253.2:c.2594G>A
  • NM_198253.3:c.2594G>AMANE SELECT
  • NP_001180305.1:p.Arg865His
  • NP_937983.2:p.Arg865His
  • NP_937983.2:p.Arg865His
  • LRG_343t1:c.2594G>A
  • LRG_343:g.33524G>A
  • LRG_343p1:p.Arg865His
  • NC_000005.9:g.1266639C>T
  • NR_149162.2:n.2491G>A
  • NR_149163.2:n.2455G>A
  • O14746:p.Arg865His
Protein change:
R865H; ARG865HIS
UniProtKB: O14746#VAR_036868; OMIM: 187270.0008; dbSNP: rs121918666
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001193376.2:c.2594G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198253.2:c.2594G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198253.3:c.2594G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149162.2:n.2491G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_149163.2:n.2455G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000490843GeneDxcriteria provided, single submitter
(Oct 18, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000490843.2

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


The R865H variant has been published previously in association with TERT-related disorders (Tsakiri et al., 2007; Fernandez et al., 2012; DiNardo et al., 2016). The variant is observed in 1/23030 (0.004%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have demonstrated that R865H results in significantly reduced enzyme activities (Tsakiri et al., 2007; Zaug et al., 2013). In summary, we consider this variant to be pathogenic.

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

Last Updated: Apr 28, 2021

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