NM_198253.3(TERT):c.2591T>C (p.Leu864Pro) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 7, 2023
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:: RCV002533689.10

Allele description [Variation Report for NM_198253.3(TERT):c.2591T>C (p.Leu864Pro)]

NM_198253.3(TERT):c.2591T>C (p.Leu864Pro)

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.2591T>C (p.Leu864Pro)

HGVS:

NC_000005.10:g.1266527A>G
NG_009265.1:g.33521T>C
NM_001193376.3:c.2591T>C
NM_198253.3:c.2591T>CMANE SELECT
NP_001180305.1:p.Leu864Pro
NP_937983.2:p.Leu864Pro
NP_937983.2:p.Leu864Pro
LRG_343t1:c.2591T>C
LRG_343:g.33521T>C
LRG_343p1:p.Leu864Pro
NC_000005.9:g.1266642A>G
NM_198253.2:c.2591T>C
NR_149162.3:n.2488T>C
NR_149163.3:n.2452T>C

Protein change:

L864P

Links:

dbSNP: rs1561194110

NCBI 1000 Genomes Browser:

rs1561194110

Molecular consequence:

NM_001193376.3:c.2591T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2591T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_149162.3:n.2488T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.2452T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita, autosomal dominant 2
Identifiers:: MONDO: MONDO:0013521; MedGen: C3151443; OMIM: 613989

Name:: Idiopathic Pulmonary Fibrosis
Synonyms:: Idiopathic fibrosing alveolitis, chronic form
Identifiers:: MeSH: D054990; MedGen: C1800706

Recent activity

Clear Turn Off Turn On

LOC110386946 [Mus musculus]
LOC110386946 [Mus musculus]
Gene ID:110386946

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000832473	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27192671, 30523342, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000832473

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 7, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Danazol Treatment for Telomere Diseases.

Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, Hardy N, Mihalek AD, Lingala S, Kim YJ, Yao J, Jones E, Gochuico BR, Heller T, Wu CO, Calado RT, Scheinberg P, Young NS.

N Engl J Med. 2016 May 19;374(20):1922-31. doi: 10.1056/NEJMoa1515319.

PubMed [citation]

PMID:: 27192671
PMCID:: PMC4968696

Pathogenic TERT promoter variants in telomere diseases.

Gutierrez-Rodrigues F, Donaires FS, Pinto A, Vicente A, Dillon LW, Clé DV, Santana BA, Pirooznia M, Ibanez MDPF, Townsley DM, Kajigaya S, Hourigan CS, Cooper JN, Calado RT, Young NS.

Genet Med. 2019 Jul;21(7):1594-1602. doi: 10.1038/s41436-018-0385-x. Epub 2018 Dec 7.

PubMed [citation]

PMID:: 30523342
PMCID:: PMC6555700

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000832473.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TERT protein function. ClinVar contains an entry for this variant (Variation ID: 580119). This missense change has been observed in individual(s) with clinical features of TERT-related telomere disease (PMID: 27192671, 30523342; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 864 of the TERT protein (p.Leu864Pro).

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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine