NM_001032283.3(TMPO):c.170C>T (p.Thr57Ile) AND Loeys-Dietz syndrome 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 26, 2022
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:: RCV002912937.2

Allele description

NM_001032283.3(TMPO):c.170C>T (p.Thr57Ile)

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.170C>T (p.Thr57Ile)

HGVS:

NC_000012.12:g.98516037C>T
NG_021393.1:g.5465C>T
NM_001032283.3:c.170C>TMANE SELECT
NM_001032284.3:c.170C>T
NM_001307975.2:c.170C>T
NM_003276.2:c.170C>T
NP_001027454.1:p.Thr57Ile
NP_001027454.1:p.Thr57Ile
NP_001027455.1:p.Thr57Ile
NP_001294904.1:p.Thr57Ile
NP_003267.1:p.Thr57Ile
LRG_443t1:c.170C>T
LRG_443t2:c.170C>T
LRG_443:g.5465C>T
LRG_443p1:p.Thr57Ile
LRG_443p2:p.Thr57Ile
NC_000012.11:g.98909815C>T
NM_001032283.2:c.170C>T
NR_027157.1:n.190G>A

Protein change:

T57I

Molecular consequence:

NM_001032283.3:c.170C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001032284.3:c.170C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001307975.2:c.170C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003276.2:c.170C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_027157.1:n.190G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Loeys-Dietz syndrome 2 (LDS2)
Synonyms:: Loeys-Dietz syndrome type 1B; MARFAN SYNDROME, TYPE II; Loeys-Dietz syndrome type 2B; 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
SCV003247736	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 26, 2022)	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

SCV003247736

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 26, 2022)

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, SCV003247736.2

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TMPO-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 57 of the TMPO protein (p.Thr57Ile).

#	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: Feb 20, 2024

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