NM_001032283.3(TMPO):c.278G>A (p.Arg93Lys) AND Loeys-Dietz syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 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:: RCV000645709.7

Allele description [Variation Report for NM_001032283.3(TMPO):c.278G>A (p.Arg93Lys)]

NM_001032283.3(TMPO):c.278G>A (p.Arg93Lys)

Genes:

LOC130008520:ATAC-STARR-seq lymphoblastoid silent region 4752 [Gene]
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.278G>A (p.Arg93Lys)

HGVS:

NC_000012.12:g.98516145G>A
NG_021393.1:g.5573G>A
NM_001032283.3:c.278G>AMANE SELECT
NM_001032284.3:c.278G>A
NM_001307975.2:c.278G>A
NM_003276.2:c.278G>A
NP_001027454.1:p.Arg93Lys
NP_001027455.1:p.Arg93Lys
NP_001294904.1:p.Arg93Lys
NP_003267.1:p.Arg93Lys
LRG_443t2:c.278G>A
LRG_443:g.5573G>A
LRG_443p2:p.Arg93Lys
NC_000012.11:g.98909923G>A
NR_027157.1:n.82C>T

Protein change:

R93K

Links:

dbSNP: rs1555201635

NCBI 1000 Genomes Browser:

rs1555201635

Molecular consequence:

NM_001032283.3:c.278G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001032284.3:c.278G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001307975.2:c.278G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003276.2:c.278G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027157.1:n.82C>T - 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
SCV000767461	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 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

SCV000767461

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000767461.5

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 93 of the TMPO protein (p.Arg93Lys). 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: 536977). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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: Feb 14, 2024

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