NM_198253.3(TERT):c.1319A>T (p.Glu440Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 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:: RCV003809003.1

Allele description [Variation Report for NM_198253.3(TERT):c.1319A>T (p.Glu440Val)]

NM_198253.3(TERT):c.1319A>T (p.Glu440Val)

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.1319A>T (p.Glu440Val)

HGVS:

NC_000005.10:g.1293567T>A
NG_009265.1:g.6481A>T
NM_001193376.3:c.1319A>T
NM_003219.1:c.1319A>T
NM_198253.3:c.1319A>TMANE SELECT
NP_001180305.1:p.Glu440Val
NP_003210.1:p.Glu440Val
NP_937983.2:p.Glu440Val
NP_937983.2:p.Glu440Val
LRG_343t1:c.1319A>T
LRG_343:g.6481A>T
LRG_343p1:p.Glu440Val
NC_000005.9:g.1293682T>A
NM_198253.2:c.1319A>T
NR_149162.3:n.1398A>T
NR_149163.3:n.1398A>T

Protein change:

E440V

Molecular consequence:

NM_001193376.3:c.1319A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003219.1:c.1319A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.1319A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_149162.3:n.1398A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.1398A>T - 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
SCV004595821	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004595821

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 15, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004595821.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TERT protein function. This variant has not been reported in the literature in individuals affected with TERT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 440 of the TERT protein (p.Glu440Val).

#	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: Jun 17, 2024

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