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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 18, 2017
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:: RCV000412959.10

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_001193376.3: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
NM_198253.2:c.2594G>A
NR_149162.3:n.2491G>A
NR_149163.3: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_001193376.3:c.2594G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2594G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_149162.3:n.2491G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.2455G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490843	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 18, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490843

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 18, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000490843.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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