NM_003238.6(TGFB2):c.619G>C (p.Val207Leu) AND not specified

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Aug 12, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000196984.20

Allele description [Variation Report for NM_003238.6(TGFB2):c.619G>C (p.Val207Leu)]

NM_003238.6(TGFB2):c.619G>C (p.Val207Leu)

Gene:

TGFB2:transforming growth factor beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_003238.6(TGFB2):c.619G>C (p.Val207Leu)

Other names:

p.V207L:GTT>CTT

HGVS:

NC_000001.11:g.218434190G>C
NG_027721.2:g.93857G>C
NM_001135599.4:c.703G>C
NM_003238.6:c.619G>CMANE SELECT
NP_001129071.1:p.Val235Leu
NP_001129071.1:p.Val235Leu
NP_003229.1:p.Val207Leu
NC_000001.10:g.218607532G>C
NM_001135599.1:c.703G>C
NM_001135599.2:c.703G>C
NM_001135599.3:c.703G>C
NM_003238.3:c.619G>C
NM_003238.4:c.619G>C
NR_138148.2:n.1985G>C
NR_138149.2:n.2069G>C

Protein change:

V207L

Links:

dbSNP: rs10482810

NCBI 1000 Genomes Browser:

rs10482810

Molecular consequence:

NM_001135599.4:c.703G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003238.6:c.619G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_138148.2:n.1985G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.2069G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000250836	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Feb 22, 2017)	germline	clinical testing	Citation Link,
SCV000309501	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000858025	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Nov 29, 2017)	germline	clinical testing	Citation Link,
SCV001362849	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Aug 12, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26017485, 28655553, 28633253 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	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

First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm.

van de Luijtgaarden KM, Heijsman D, Maugeri A, Weiss MM, Verhagen HJ, IJpma A, Brüggenwirth HT, Majoor-Krakauer D.

Hum Genet. 2015 Aug;134(8):881-93. doi: 10.1007/s00439-015-1567-0. Epub 2015 May 28.

PubMed [citation]

PMID:: 26017485
PMCID:: PMC4495250

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000250836.8

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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

From PreventionGenetics, part of Exact Sciences, SCV000309501.1

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

#	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

From Eurofins Ntd Llc (ga), SCV000858025.1

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

#	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		1	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362849.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: TGFB2 c.619G>C (p.Val207Leu) results in a conservative amino acid change located in the TGF-beta propeptide domain (IPR001111) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0033 in 251286 control chromosomes, predominantly at a frequency of 0.005 within the Non-Finnish European subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 400 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFB2 causing Aortopathy phenotype (1.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.619G>C has been reported in the literature in individuals affected with aortic root dilation, vascular anomalies and familial abdominal aortic aneurysm (Disha_2017, vandeLuijtgaarden_2015, Mattassi_2018) without strong evidence of causality. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (9x Likely benign/benign and 1x uncertain significance). Based on the evidence outlined above, the variant was classified as likely benign.

#	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: Apr 20, 2024

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