NM_001032283.3(TMPO):c.565+995_565+998del AND Loeys-Dietz syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 25, 2024
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:: RCV001920720.7

Allele description [Variation Report for NM_001032283.3(TMPO):c.565+995_565+998del]

NM_001032283.3(TMPO):c.565+995_565+998del

Gene:

TMPO:thymopoietin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

12q23.1

Genomic location:

Preferred name:

NM_001032283.3(TMPO):c.565+995_565+998del

HGVS:

NC_000012.12:g.98532829AGAA[1]
NG_021393.1:g.22257AGAA[1]
NM_001032283.3:c.565+995_565+998delMANE SELECT
NM_001032284.3:c.565+995_565+998del
NM_001307975.2:c.565+995_565+998del
NM_003276.2:c.576_579del
NP_003267.1:p.Lys192fs
LRG_443t2:c.576_579del
LRG_443:g.22257AGAA[1]
LRG_443p2:p.Lys192fs
NC_000012.11:g.98926606_98926609del
NC_000012.11:g.98926607AGAA[1]

Protein change:

K192fs

Links:

dbSNP: rs747695132

NCBI 1000 Genomes Browser:

rs747695132

Molecular consequence:

NM_003276.2:c.576_579del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001032283.3:c.565+995_565+998del - intron variant - [Sequence Ontology: SO:0001627]
NM_001032284.3:c.565+995_565+998del - intron variant - [Sequence Ontology: SO:0001627]
NM_001307975.2:c.565+995_565+998del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Loeys-Dietz syndrome 2 (LDS2)
Synonyms:: AORTIC ANEURYSM, FAMILIAL THORACIC 3; MARFAN SYNDROME, TYPE II; Marfan syndrome, type 2 (formerly); 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
SCV002186549	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	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

SCV002186549

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2024)

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, SCV002186549.4

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

Description

This sequence change creates a premature translational stop signal (p.Lys192Asnfs*5) in the TMPO gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 503 amino acid(s) of the TMPO protein. This variant is present in population databases (rs747695132, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1411579). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: Jan 17, 2026

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