NM_003242.6(TGFBR2):c.1043G>A (p.Arg348His) AND Loeys-Dietz syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV004003501.2

Allele description [Variation Report for NM_003242.6(TGFBR2):c.1043G>A (p.Arg348His)]

NM_003242.6(TGFBR2):c.1043G>A (p.Arg348His)

Gene:

TGFBR2:transforming growth factor beta receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.1043G>A (p.Arg348His)

HGVS:

NC_000003.12:g.30672226G>A
NG_007490.1:g.70725G>A
NM_001024847.3:c.1118G>A
NM_001407126.1:c.1226G>A
NM_001407127.1:c.1151G>A
NM_001407128.1:c.1070G>A
NM_001407129.1:c.1046G>A
NM_001407130.1:c.1043G>A
NM_001407132.1:c.938G>A
NM_001407133.1:c.938G>A
NM_001407134.1:c.938G>A
NM_001407135.1:c.938G>A
NM_001407136.1:c.938G>A
NM_001407137.1:c.758G>A
NM_001407138.1:c.683G>A
NM_003242.6:c.1043G>AMANE SELECT
NP_001020018.1:p.Arg373His
NP_001020018.1:p.Arg373His
NP_001394055.1:p.Arg409His
NP_001394056.1:p.Arg384His
NP_001394057.1:p.Arg357His
NP_001394058.1:p.Arg349His
NP_001394059.1:p.Arg348His
NP_001394061.1:p.Arg313His
NP_001394062.1:p.Arg313His
NP_001394063.1:p.Arg313His
NP_001394064.1:p.Arg313His
NP_001394065.1:p.Arg313His
NP_001394066.1:p.Arg253His
NP_001394067.1:p.Arg228His
NP_003233.4:p.Arg348His
LRG_779t1:c.1118G>A
LRG_779t2:c.1043G>A
LRG_779:g.70725G>A
LRG_779p1:p.Arg373His
LRG_779p2:p.Arg348His
NC_000003.11:g.30713718G>A
NM_001024847.2:c.1118G>A
NM_003242.5:c.1043G>A

Protein change:

R228H

Links:

dbSNP: rs369450067

NCBI 1000 Genomes Browser:

rs369450067

Molecular consequence:

NM_001024847.3:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.1151G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.1070G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.1046G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.758G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.683G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

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trigger factor [Corynebacterium diphtheriae]
trigger factor [Corynebacterium diphtheriae]
gi|504086371|ref|WP_014320365.1|

Protein
086190_3008_2496 Arabidopsis ovule high throughput cDNA library Arabidopsis thal...
086190_3008_2496 Arabidopsis ovule high throughput cDNA library Arabidopsis thaliana cDNA, mRNA sequence
gi|164059640|gnl|dbEST|45540407|gb| 259.1|

Nucleotide
307443_3804_2835 Arabidopsis ovule high throughput cDNA library Arabidopsis thal...
307443_3804_2835 Arabidopsis ovule high throughput cDNA library Arabidopsis thaliana cDNA, mRNA sequence
gi|164046977|gnl|dbEST|45700372|gb| 224.1|

Nucleotide
alkylated DNA repair protein alkB homolog 8 isoform 1 [Homo sapiens]
alkylated DNA repair protein alkB homolog 8 isoform 1 [Homo sapiens]
gi|195927056|ref|NP_620130.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004839220	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Sep 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18781618, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004839220

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Sep 18, 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	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders.

Stheneur C, Collod-Béroud G, Faivre L, Gouya L, Sultan G, Le Parc JM, Moura B, Attias D, Muti C, Sznajder M, Claustres M, Junien C, Baumann C, Cormier-Daire V, Rio M, Lyonnet S, Plauchu H, Lacombe D, Chevallier B, Jondeau G, Boileau C.

Hum Mutat. 2008 Nov;29(11):E284-95. doi: 10.1002/humu.20871.

PubMed [citation]

PMID:: 18781618

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004839220.1

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

Description

This missense variant replaces arginine with histidine at codon 348 of the TGFBR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual suspected with Marfan syndrome or related disorders (PMID: 18781618). This variant has been identified in 10/280264 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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