NM_001032283.3(TMPO):c.152C>T (p.Pro51Leu) AND Loeys-Dietz syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 26, 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:: RCV003626761.3

Allele description [Variation Report for NM_001032283.3(TMPO):c.152C>T (p.Pro51Leu)]

NM_001032283.3(TMPO):c.152C>T (p.Pro51Leu)

Genes:

TMPO-AS1:TMPO antisense RNA 1 [Gene - HGNC]
TMPO:thymopoietin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.1

Genomic location:

Preferred name:

NM_001032283.3(TMPO):c.152C>T (p.Pro51Leu)

HGVS:

NC_000012.12:g.98516019C>T
NG_021393.1:g.5447C>T
NM_001032283.3:c.152C>TMANE SELECT
NM_001032284.3:c.152C>T
NM_001307975.2:c.152C>T
NM_003276.2:c.152C>T
NP_001027454.1:p.Pro51Leu
NP_001027454.1:p.Pro51Leu
NP_001027455.1:p.Pro51Leu
NP_001294904.1:p.Pro51Leu
NP_003267.1:p.Pro51Leu
LRG_443t1:c.152C>T
LRG_443t2:c.152C>T
LRG_443:g.5447C>T
LRG_443p1:p.Pro51Leu
LRG_443p2:p.Pro51Leu
NC_000012.11:g.98909797C>T
NM_001032283.2:c.152C>T
NR_027157.1:n.208G>A

Protein change:

P51L

Molecular consequence:

NM_001032283.3:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001032284.3:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001307975.2:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003276.2:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_027157.1:n.208G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Loeys-Dietz syndrome 2 (LDS2)
Synonyms:: Loeys-Dietz syndrome type 1B; AORTIC ANEURYSM, FAMILIAL THORACIC 3; MARFAN SYNDROME, TYPE II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012427; MedGen: C2674574; Orphanet: 558; OMIM: 610168

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004511629	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 26, 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

SCV004511629

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 26, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004511629.2

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

Description

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1774591). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 51 of the TMPO protein (p.Pro51Leu). 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: Mar 5, 2025

ClinVar

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