NM_004612.4(TGFBR1):c.1238G>A (p.Arg413Gln) AND Loeys-Dietz syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV004005741.2

Allele description [Variation Report for NM_004612.4(TGFBR1):c.1238G>A (p.Arg413Gln)]

NM_004612.4(TGFBR1):c.1238G>A (p.Arg413Gln)

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.1238G>A (p.Arg413Gln)

HGVS:

NC_000009.12:g.99146592G>A
NG_007461.1:g.46463G>A
NM_001130916.3:c.1007G>A
NM_001306210.2:c.1250G>A
NM_001407416.1:c.1082G>A
NM_001407417.1:c.1070G>A
NM_001407418.1:c.1043G>A
NM_001407419.1:c.1043G>A
NM_001407420.1:c.1043G>A
NM_001407422.1:c.1043G>A
NM_001407423.1:c.1031G>A
NM_001407424.1:c.1031G>A
NM_001407425.1:c.1031G>A
NM_001407426.1:c.1031G>A
NM_001407427.1:c.1031G>A
NM_001407428.1:c.1031G>A
NM_001407429.1:c.1031G>A
NM_001407430.1:c.1031G>A
NM_001407432.1:c.1031G>A
NM_001407433.1:c.1031G>A
NM_001407434.1:c.1031G>A
NM_001407435.1:c.1007G>A
NM_001407436.1:c.992G>A
NM_001407437.1:c.530G>A
NM_001407438.1:c.761G>A
NM_004612.4:c.1238G>AMANE SELECT
NP_001124388.1:p.Arg336Gln
NP_001293139.1:p.Arg417Gln
NP_001394345.1:p.Arg361Gln
NP_001394346.1:p.Arg357Gln
NP_001394347.1:p.Arg348Gln
NP_001394348.1:p.Arg348Gln
NP_001394349.1:p.Arg348Gln
NP_001394351.1:p.Arg348Gln
NP_001394352.1:p.Arg344Gln
NP_001394353.1:p.Arg344Gln
NP_001394354.1:p.Arg344Gln
NP_001394355.1:p.Arg344Gln
NP_001394356.1:p.Arg344Gln
NP_001394357.1:p.Arg344Gln
NP_001394358.1:p.Arg344Gln
NP_001394359.1:p.Arg344Gln
NP_001394361.1:p.Arg344Gln
NP_001394362.1:p.Arg344Gln
NP_001394363.1:p.Arg344Gln
NP_001394364.1:p.Arg336Gln
NP_001394365.1:p.Arg331Gln
NP_001394366.1:p.Arg177Gln
NP_001394367.1:p.Arg254Gln
NP_004603.1:p.Arg413Gln
NC_000009.11:g.101908874G>A
NM_004612.2:c.1238G>A
NR_176361.1:n.1447G>A

Protein change:

R177Q

Molecular consequence:

NM_001130916.3:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306210.2:c.1250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407416.1:c.1082G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407417.1:c.1070G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407418.1:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407419.1:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407420.1:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407422.1:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407423.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407424.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407425.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407426.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407427.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407428.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407429.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407430.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407432.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407433.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407434.1:c.1031G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407435.1:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407436.1:c.992G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407437.1:c.530G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407438.1:c.761G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004612.4:c.1238G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004828915	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 28, 2023)	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

SCV004828915

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 28, 2023)

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	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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, SCV004828915.1

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

Description

This missense variant replaces arginine with glutamine at codon 413 of the TGFBR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TGFBR1-related disorders in the literature. This variant has been identified in 1/251156 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: May 7, 2024

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