NM_001130144.3(LTBP3):c.2328del (p.Ala777fs) AND Brachyolmia-amelogenesis imperfecta syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV003755795.2

Allele description [Variation Report for NM_001130144.3(LTBP3):c.2328del (p.Ala777fs)]

NM_001130144.3(LTBP3):c.2328del (p.Ala777fs)

Genes:

LOC130006029:ATAC-STARR-seq lymphoblastoid silent region 3532 [Gene]
LTBP3:latent transforming growth factor beta binding protein 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001130144.3(LTBP3):c.2328del (p.Ala777fs)

HGVS:

NC_000011.10:g.65546469del
NG_016437.1:g.16762del
NG_185474.1:g.259del
NM_001130144.3:c.2328delMANE SELECT
NM_001164266.1:c.1977del
NM_021070.4:c.2328del
NP_001123616.1:p.Ala777fs
NP_001157738.1:p.Ala660fs
NP_066548.2:p.Ala777fs
NC_000011.9:g.65313938del
NC_000011.9:g.65313940del

Protein change:

A660fs

Molecular consequence:

NM_001130144.3:c.2328del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001164266.1:c.1977del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021070.4:c.2328del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Brachyolmia-amelogenesis imperfecta syndrome
Synonyms:: Verloes Bourguignon syndrome; Skeletal dysplasia with amelogenesis imperfecta and platyspondyly; Platyspondyly with amelogenesis imperfecta; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011018; MedGen: C1832594; Orphanet: 2899; OMIM: 601216

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004450577	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11790802, 19344874, 25669657, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004450577

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Bone abnormalities in latent TGF-[beta] binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-[beta] bioavailability.

Dabovic B, Chen Y, Colarossi C, Obata H, Zambuto L, Perle MA, Rifkin DB.

J Cell Biol. 2002 Jan 21;156(2):227-32. Epub 2002 Jan 14.

PubMed [citation]

PMID:: 11790802
PMCID:: PMC2199217

Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3.

Noor A, Windpassinger C, Vitcu I, Orlic M, Rafiq MA, Khalid M, Malik MN, Ayub M, Alman B, Vincent JB.

Am J Hum Genet. 2009 Apr;84(4):519-23. doi: 10.1016/j.ajhg.2009.03.007. Epub 2009 Apr 2.

PubMed [citation]

PMID:: 19344874
PMCID:: PMC2667979

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004450577.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala777Argfs*91) in the LTBP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LTBP3 are known to be pathogenic (PMID: 11790802, 19344874, 25669657).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine