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NM_004612.4(TGFBR1):c.3_27dup (p.Pro10fs) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 8, 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:
RCV003529731.2

Allele description [Variation Report for NM_004612.4(TGFBR1):c.3_27dup (p.Pro10fs)]

NM_004612.4(TGFBR1):c.3_27dup (p.Pro10fs)

Genes:
LOC130002223:ATAC-STARR-seq lymphoblastoid silent region 20124 [Gene]
TGFBR1:transforming growth factor beta receptor 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
9q22.33
Genomic location:
Preferred name:
NM_004612.4(TGFBR1):c.3_27dup (p.Pro10fs)
HGVS:
  • NC_000009.12:g.99105208_99105232dup
  • NG_007461.1:g.5079_5103dup
  • NG_181669.1:g.668_692dup
  • NM_001130916.3:c.3_27dup
  • NM_001306210.2:c.3_27dup
  • NM_001407416.1:c.3_27dup
  • NM_001407417.1:c.3_27dup
  • NM_001407418.1:c.-111+1467_-111+1491dup
  • NM_001407419.1:c.-111+83_-111+107dup
  • NM_001407420.1:c.-341_-317dup
  • NM_001407422.1:c.-310_-286dup
  • NM_001407423.1:c.-111+1467_-111+1491dup
  • NM_001407424.1:c.-111+1102_-111+1126dup
  • NM_001407425.1:c.-111+689_-111+713dup
  • NM_001407426.1:c.-310_-286dup
  • NM_001407428.1:c.-265_-241dup
  • NM_001407429.1:c.-341_-317dup
  • NM_001407432.1:c.-247+83_-247+107dup
  • NM_001407433.1:c.-111+83_-111+107dup
  • NM_001407434.1:c.-111+482_-111+506dup
  • NM_001407435.1:c.3_27dup
  • NM_001407436.1:c.3_27dup
  • NM_001407437.1:c.3_27dup
  • NM_001407438.1:c.3_27dup
  • NM_004612.4:c.3_27dupMANE SELECT
  • NP_001124388.1:p.Pro10fs
  • NP_001293139.1:p.Pro10fs
  • NP_001394345.1:p.Pro10fs
  • NP_001394346.1:p.Pro10fs
  • NP_001394364.1:p.Pro10fs
  • NP_001394365.1:p.Pro10fs
  • NP_001394366.1:p.Pro10fs
  • NP_001394367.1:p.Pro10fs
  • NP_004603.1:p.Pro10fs
  • NC_000009.11:g.101867488_101867489insTGGAGGCGGCGGTCGCTGCTCCGCG
  • NC_000009.11:g.101867490_101867514dup
  • NR_176360.1:n.96_120dup
  • NR_176361.1:n.96_120dup
  • NR_176362.1:n.96_120dup
  • NR_176363.1:n.96_120dup
Protein change:
P10fs
Molecular consequence:
  • NM_001407420.1:c.-341_-317dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407422.1:c.-310_-286dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407426.1:c.-310_-286dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407428.1:c.-265_-241dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407429.1:c.-341_-317dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001130916.3:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001306210.2:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407416.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407417.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407435.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407436.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407437.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407438.1:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004612.4:c.3_27dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001130916.3:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001306210.2:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407416.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407417.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407435.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407436.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407437.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407438.1:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_004612.4:c.3_27dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001407418.1:c.-111+1467_-111+1491dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407419.1:c.-111+83_-111+107dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407423.1:c.-111+1467_-111+1491dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407424.1:c.-111+1102_-111+1126dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407425.1:c.-111+689_-111+713dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407432.1:c.-247+83_-247+107dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407433.1:c.-111+83_-111+107dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407434.1:c.-111+482_-111+506dup - intron variant - [Sequence Ontology: SO:0001627]
  • NR_176360.1:n.96_120dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176361.1:n.96_120dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176362.1:n.96_120dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176363.1:n.96_120dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004314735Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 8, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.

Goudie DR, D'Alessandro M, Merriman B, Lee H, Szeverényi I, Avery S, O'Connor BD, Nelson SF, Coats SE, Stewart A, Christie L, Pichert G, Friedel J, Hayes I, Burrows N, Whittaker S, Gerdes AM, Broesby-Olsen S, Ferguson-Smith MA, Verma C, Lunny DP, Reversade B, et al.

Nat Genet. 2011 Feb 27;43(4):365-9. doi: 10.1038/ng.780.

PubMed [citation]
PMID:
21358634

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004314735.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Pro10Glyfs*73) in the TGFBR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGFBR1 are known to be pathogenic (PMID: 21358634).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024