NM_198253.3(TERT):c.1174_1175del (p.Leu392fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 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:: RCV003778225.2

Allele description [Variation Report for NM_198253.3(TERT):c.1174_1175del (p.Leu392fs)]

NM_198253.3(TERT):c.1174_1175del (p.Leu392fs)

Gene:

TERT:telomerase reverse transcriptase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_198253.3(TERT):c.1174_1175del (p.Leu392fs)

HGVS:

NC_000005.10:g.1293711_1293712del
NG_009265.1:g.6336_6337del
NM_001193376.3:c.1174_1175del
NM_003219.1:c.1174_1175delCT
NM_198253.3:c.1174_1175delMANE SELECT
NP_001180305.1:p.Leu392fs
NP_003210.1:p.Leu392Valfs
NP_937983.2:p.Leu392Valfs
NP_937983.2:p.Leu392fs
LRG_343t1:c.1174_1175del
LRG_343:g.6336_6337del
LRG_343p1:p.Leu392Valfs
NC_000005.9:g.1293826_1293827del
NM_198253.2:c.1174_1175delCT
NR_149162.3:n.1253_1254del
NR_149163.3:n.1253_1254del

Protein change:

L392fs

Molecular consequence:

NM_001193376.3:c.1174_1175del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003219.1:c.1174_1175delCT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198253.3:c.1174_1175del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_149162.3:n.1253_1254del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.1253_1254del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004587105	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16247010, 17460043, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004587105

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 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

Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.

Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW.

Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15960-4. Epub 2005 Oct 24.

PubMed [citation]

PMID:: 16247010
PMCID:: PMC1276104

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004587105.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with pulmonary fibrosis (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu392Valfs*146) in the TERT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TERT are known to be pathogenic (PMID: 16247010, 17460043).

#	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: Sep 29, 2024

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