This variant results in an amino acid alteration replacing a lysine (K) with a serine (S) at position 128 creating a premature stop signal in the new reading frame noted as p K128Sfs*35. The substitution is predicted to result in a non-functional TGFBR2 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH, Bethesda MD), but it has been described in 3478 alleles out of 85936, in the ExAC database, all of them belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Conflicting interpretations of pathogenicity
Likely pathogenic(1); Benign(3); Likely benign(1)
- Review status:
- criteria provided, conflicting interpretations
- Submissions:
- 8
- First in ClinVar:
- Dec 26, 2017
- Most recent Submission:
- Mar 26, 2023
- Last evaluated:
- Nov 14, 2021
- Accession:
- VCV000477546.21
- Variation ID:
- 477546
- Description:
- 1bp deletion
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NM_003242.6(TGFBR2):c.383del (p.Lys128fs)
- Allele ID
- 452306
- Variant type
- Deletion
- Variant length
- 1 bp
- Cytogenetic location
- 3p24.1
- Genomic location
- 3: 30650380 (GRCh38) GRCh38 UCSC
- 3: 30691872 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003242.6:c.383del MANE Select NP_003233.4:p.Lys128fs frameshift NM_001024847.3:c.458delA NP_001020018.1:p.Lys153Serfs frameshift NM_001407126.1:c.458delA NP_001394055.1:p.Lys153Serfs frameshift NM_001407127.1:c.383delA NP_001394056.1:p.Lys128Serfs frameshift NM_001407128.1:c.410delA NP_001394057.1:p.Lys137Serfs frameshift NM_001407129.1:c.278delA NP_001394058.1:p.Lys93Serfs frameshift NM_001407130.1:c.383delA NP_001394059.1:p.Lys128Serfs frameshift NM_001407132.1:c.278delA NP_001394061.1:p.Lys93Serfs frameshift NM_001407133.1:c.278delA NP_001394062.1:p.Lys93Serfs frameshift NM_001407134.1:c.278delA NP_001394063.1:p.Lys93Serfs frameshift NM_001407135.1:c.278delA NP_001394064.1:p.Lys93Serfs frameshift NM_001407136.1:c.278delA NP_001394065.1:p.Lys93Serfs frameshift NM_001407139.1:c.458delA NP_001394068.1:p.Lys153Serfs frameshift NM_003242.5:c.383del NC_000003.12:g.30650389del NC_000003.11:g.30691881del NG_007490.1:g.48888del LRG_779:g.48888del LRG_779t1:c.458del LRG_779p1:p.Lys153fs LRG_779t2:c.383del LRG_779p2:p.Lys128fs - Protein change
- K153fs, K128fs
- Other names
- -
- Canonical SPDI
- NC_000003.12:30650379:AAAAAAAAAA:AAAAAAAAA
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA048107
- dbSNP: rs79375991
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Benign/Likely benign | 3 | criteria provided, multiple submitters, no conflicts | Nov 14, 2021 | RCV000559144.8 | |
| Likely pathogenic | 1 | criteria provided, single submitter | Mar 10, 2018 | RCV000680445.2 | |
| Benign | 3 | criteria provided, single submitter | Feb 9, 2019 | RCV001001460.11 | |
| Likely benign | 1 | no assertion criteria provided | - | RCV001702809.2 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| TGFBR2 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
903 | 921 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Likely pathogenic
(Mar 10, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Loeys-Dietz syndrome
Affected status: no
Allele origin:
germline
|
GeneID Lab - Advanced Molecular Diagnostics
Accession: SCV000807818.1
First in ClinVar: Sep 24, 2018 Last updated: Sep 24, 2018 |
Comment:
This variant results in an amino acid alteration replacing a lysine (K) with a serine (S) at position 128 creating a premature stop signal in … (more)
This variant results in an amino acid alteration replacing a lysine (K) with a serine (S) at position 128 creating a premature stop signal in the new reading frame noted as p K128Sfs*35. The substitution is predicted to result in a non-functional TGFBR2 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH, Bethesda MD), but it has been described in 3478 alleles out of 85936, in the ExAC database, all of them belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant. (less)
Number of individuals with the variant: 1
Age: 20-29 years
Sex: female
Ethnicity/Population group: Latin American
Geographic origin: United States
|
|
|
Benign
(Feb 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158709.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
|
|
|
Likely benign
(Jun 25, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001735851.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
|
|
Benign
(May 06, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000739846.4
First in ClinVar: Apr 16, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
|
|
|
Benign
(Nov 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000658831.2
First in ClinVar: Dec 26, 2017 Last updated: Mar 26, 2023 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740432.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928220.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965452.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs79375991...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Mar 26, 2023