NM_198253.3(TERT):c.2593C>T (p.Arg865Cys) AND multiple conditions

delete

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 22, 2018
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:: RCV002451631.8

Allele description

NM_198253.3(TERT):c.2593C>T (p.Arg865Cys)

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.2593C>T (p.Arg865Cys)

HGVS:

NC_000005.10:g.1266525G>A
NG_009265.1:g.33523C>T
NM_001193376.3:c.2593C>T
NM_198253.3:c.2593C>TMANE SELECT
NP_001180305.1:p.Arg865Cys
NP_937983.2:p.Arg865Cys
LRG_343t1:c.2593C>T
LRG_343:g.33523C>T
NC_000005.9:g.1266640G>A
NM_198253.2:c.2593C>T
NR_149162.3:n.2490C>T
NR_149163.3:n.2454C>T

Protein change:

R865C

Links:

dbSNP: rs372868296

NCBI 1000 Genomes Browser:

rs372868296

Molecular consequence:

NM_001193376.3:c.2593C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2593C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_149162.3:n.2490C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.2454C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002739391	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Dec 22, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17460043, 20502709, 22364217, 27540018 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002739391

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Dec 22, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Adult-onset pulmonary fibrosis caused by mutations in telomerase.

Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK.

Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7. Epub 2007 Apr 25.

PubMed [citation]

PMID:: 17460043
PMCID:: PMC1855917

Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations.

Diaz de Leon A, Cronkhite JT, Katzenstein AL, Godwin JD, Raghu G, Glazer CS, Rosenblatt RL, Girod CE, Garrity ER, Xing C, Garcia CK.

PLoS One. 2010 May 19;5(5):e10680. doi: 10.1371/journal.pone.0010680.

PubMed [citation]

PMID:: 20502709
PMCID:: PMC2873288

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002739391.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The p.R865C variant (also known as c.2593C>T), located in coding exon 10 of the TERT gene, results from a C to T substitution at nucleotide position 2593. The arginine at codon 865 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was identified in an individual with pulmonary fibrosis, neutropenia, and shortened telomere length (Tsakiri KD et al. Proc. Natl. Acad. Sci. U.S.A., 2007 May;104:7552-7; Diaz de Leon A et al. PLoS ONE, 2010 May;5:e10680; Newton CA et al. Eur. Respir. J., 2016 12;48:1710-1720). Telomerase activity analysis in vitro and in human cells demonstrated a reduced activity compared to wild type (Tsang AR et al. Aging Cell, 2012 Jun;11:482-90). A disease-causing mutation, p.R865H, has been described in the same codon (Tsakiri KD et al. Proc. Natl. Acad. Sci. U.S.A., 2007 May;104:7552-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Jun 2, 2024

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