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:
current
Accession:
RCV000412959.2

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

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

Gene:
TERT:telomerase reverse transcriptase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p15.33
Genomic location:
Preferred name:
NM_198253.3(TERT):c.2594G>A (p.Arg865His)
HGVS:
  • 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
Links:
UniProtKB: O14746#VAR_036868; OMIM: 187270.0008; dbSNP: rs121918666
NCBI 1000 Genomes Browser:
rs121918666
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]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000490843GeneDxcriteria provided, single submitter
Pathogenic
(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

Description

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.

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

Last Updated: Apr 28, 2021

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