U.S. flag

An official website of the United States government

NM_003242.6(TGFBR2):c.1583G>A (p.Arg528His) AND Loeys-Dietz syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 29, 2014
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:
RCV000211858.5

Allele description [Variation Report for NM_003242.6(TGFBR2):c.1583G>A (p.Arg528His)]

NM_003242.6(TGFBR2):c.1583G>A (p.Arg528His)

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.1583G>A (p.Arg528His)
Other names:
p.R528H:CGT>CAT
HGVS:
  • NC_000003.12:g.30691478G>A
  • NG_007490.1:g.89977G>A
  • NM_001024847.3:c.1658G>A
  • NM_001407126.1:c.1766G>A
  • NM_001407127.1:c.1691G>A
  • NM_001407128.1:c.1610G>A
  • NM_001407129.1:c.1586G>A
  • NM_001407130.1:c.1580G>A
  • NM_001407132.1:c.1478G>A
  • NM_001407133.1:c.1478G>A
  • NM_001407134.1:c.1478G>A
  • NM_001407135.1:c.1478G>A
  • NM_001407136.1:c.1478G>A
  • NM_001407137.1:c.1298G>A
  • NM_001407138.1:c.1223G>A
  • NM_001407139.1:c.713G>A
  • NM_003242.6:c.1583G>AMANE SELECT
  • NP_001020018.1:p.Arg553His
  • NP_001020018.1:p.Arg553His
  • NP_001394055.1:p.Arg589His
  • NP_001394056.1:p.Arg564His
  • NP_001394057.1:p.Arg537His
  • NP_001394058.1:p.Arg529His
  • NP_001394059.1:p.Arg527His
  • NP_001394061.1:p.Arg493His
  • NP_001394062.1:p.Arg493His
  • NP_001394063.1:p.Arg493His
  • NP_001394064.1:p.Arg493His
  • NP_001394065.1:p.Arg493His
  • NP_001394066.1:p.Arg433His
  • NP_001394067.1:p.Arg408His
  • NP_001394068.1:p.Arg238His
  • NP_003233.4:p.Arg528His
  • LRG_779t1:c.1658G>A
  • LRG_779t2:c.1583G>A
  • LRG_779:g.89977G>A
  • LRG_779p1:p.Arg553His
  • LRG_779p2:p.Arg528His
  • NC_000003.11:g.30732970G>A
  • NM_001024847.2:c.1658G>A
  • NM_003242.5:c.1583G>A
  • P37173:p.Arg528His
Protein change:
R238H; ARG528HIS
Links:
UniProtKB: P37173#VAR_022361; OMIM: 190182.0011; dbSNP: rs104893815
NCBI 1000 Genomes Browser:
rs104893815
Molecular consequence:
  • NM_001024847.3:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407126.1:c.1766G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407127.1:c.1691G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407128.1:c.1610G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407129.1:c.1586G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407130.1:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407132.1:c.1478G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407133.1:c.1478G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407134.1:c.1478G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407135.1:c.1478G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407136.1:c.1478G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407137.1:c.1298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407138.1:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407139.1:c.713G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003242.6:c.1583G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Loeys-Dietz syndrome (LDS)
Identifiers:
MONDO: MONDO:0018954; MedGen: C2697932; OMIM: PS609192

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000203966Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Pathogenic
(Aug 29, 2014)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.

Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, et al.

Nat Genet. 2005 Mar;37(3):275-81. Epub 2005 Jan 30.

PubMed [citation]
PMID:
15731757

Aneurysm syndromes caused by mutations in the TGF-beta receptor.

Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC.

N Engl J Med. 2006 Aug 24;355(8):788-98.

PubMed [citation]
PMID:
16928994
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000203966.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (3)

Description

The Arg528His variant in TGFBR2 has been identified in >8 individuals with Loeys -Dietz syndrome and was found to occur de novo in one of these individuals (Loey s 2005, Loeys 2006, LMM unpublished data). It was absent from large population s tudies. In vitro and in vivo functional studies provide evidence that the Arg528 His variant may impact protein function. Computational prediction tools and cons ervation analysis suggest that the Arg528His variant may impact the protein, tho ugh this information is not predictive enough to determine pathogenicity. In sum mary, this variant meets our criteria to be classified as pathogenic (http://pcp gm.partners.org/LMM).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Sep 29, 2024