NM_004612.4(TGFBR1):c.722C>T (p.Ser241Leu) AND Loeys-Dietz syndrome 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 5, 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:: RCV000013350.26

Allele description [Variation Report for NM_004612.4(TGFBR1):c.722C>T (p.Ser241Leu)]

NM_004612.4(TGFBR1):c.722C>T (p.Ser241Leu)

Gene:

TGFBR1:transforming growth factor beta receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.33

Genomic location:

Preferred name:

NM_004612.4(TGFBR1):c.722C>T (p.Ser241Leu)

HGVS:

NC_000009.12:g.99138006C>T
NG_007461.1:g.37877C>T
NM_001130916.3:c.491C>T
NM_001306210.2:c.734C>T
NM_004612.4:c.722C>TMANE SELECT
NP_001124388.1:p.Ser164Leu
NP_001293139.1:p.Ser245Leu
NP_004603.1:p.Ser241Leu
NC_000009.11:g.101900288C>T
NM_004612.2:c.722C>T
P36897:p.Ser241Leu

Protein change:

S164L; SER241LEU

Links:

UniProtKB: P36897#VAR_029482; OMIM: 190181.0005; dbSNP: rs111854391

NCBI 1000 Genomes Browser:

rs111854391

Molecular consequence:

NM_001130916.3:c.491C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001306210.2:c.734C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004612.4:c.722C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

variation affecting protein function [Variation Ontology: 0003]

Condition(s)

Name:: Loeys-Dietz syndrome 1 (LDS1)
Synonyms:: Loeys-Dietz syndrome type 1A; Furlong syndrome; Aortic aneurysm syndrome, Loeys-Dietz type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012212; MedGen: C4551955; Orphanet: 60030; OMIM: 609192

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033597	OMIM	no assertion criteria provided	Pathogenic (May 15, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002583254	Center of Excellence for Medical Genomics, Chulalongkorn University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 5, 2022)	germline	research	PubMed (2) [See all records that cite these PMIDs] 16596670, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033597

OMIM

no assertion criteria provided

Pathogenic
(May 15, 2006)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002583254

Center of Excellence for Medical Genomics, Chulalongkorn University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 5, 2022)

germline

research

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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.

Adès LC, Sullivan K, Biggin A, Haan EA, Brett M, Holman KJ, Dixon J, Robertson S, Holmes AD, Rogers J, Bennetts B.

Am J Med Genet A. 2006 May 15;140(10):1047-58.

PubMed [citation]

PMID:: 16596670

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 OMIM, SCV000033597.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 patients judged to have Furlong syndrome (see LDS1, 609192), Ades et al. (2006) found an identical heterozygous missense mutation, ser241 to leu (S241L), in the TGFBR1 gene. The mutation, which arose from a C-to-T transition at nucleotide position 722, alters a highly conserved nonpolar serine in the serine-threonine kinase domain to a polar leucine residue.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center of Excellence for Medical Genomics, Chulalongkorn University, SCV002583254.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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