NM_198253.3(TERT):c.2312C>T (p.Pro771Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 14, 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:: RCV003771871.2

Allele description [Variation Report for NM_198253.3(TERT):c.2312C>T (p.Pro771Leu)]

NM_198253.3(TERT):c.2312C>T (p.Pro771Leu)

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.2312C>T (p.Pro771Leu)

Other names:

p.Phe555Cys

HGVS:

NC_000005.10:g.1272255G>A
NG_009265.1:g.27793C>T
NM_001193376.3:c.2312C>T
NM_198253.3:c.2312C>TMANE SELECT
NP_001180305.1:p.Pro771Leu
NP_937983.2:p.Pro771Leu
LRG_343:g.27793C>T
NC_000005.9:g.1272370G>A

Protein change:

P771L

Links:

dbSNP: rs1309399887

NCBI 1000 Genomes Browser:

rs1309399887

Molecular consequence:

NM_001193376.3:c.2312C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2312C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004576963	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34019641, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004576963

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 14, 2023)

germline

clinical testing

PubMed (2)
[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

The clinical and functional effects of TERT variants in myelodysplastic syndrome.

Reilly CR, Myllymäki M, Redd R, Padmanaban S, Karunakaran D, Tesmer V, Tsai FD, Gibson CJ, Rana HQ, Zhong L, Saber W, Spellman SR, Hu ZH, Orr EH, Chen MM, De Vivo I, DeAngelo DJ, Cutler C, Antin JH, Neuberg D, Garber JE, Nandakumar J, et al.

Blood. 2021 Sep 9;138(10):898-911. doi: 10.1182/blood.2021011075.

PubMed [citation]

PMID:: 34019641
PMCID:: PMC8432045

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004576963.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 1297703). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 771 of the TERT protein (p.Pro771Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myelodysplastic syndrome (PMID: 34019641). 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. Experimental studies have shown that this missense change affects TERT function (PMID: 34019641). 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.

#	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

ClinVar

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