NM_003573.2(LTBP4):c.254del (p.Leu85fs) AND Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2014
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:: RCV000169666.14

Allele description [Variation Report for NM_003573.2(LTBP4):c.254del (p.Leu85fs)]

NM_003573.2(LTBP4):c.254del (p.Leu85fs)

Gene:

LTBP4:latent transforming growth factor beta binding protein 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_003573.2(LTBP4):c.254del (p.Leu85fs)

HGVS:

NC_000019.10:g.40600091del
NG_021201.1:g.11926del
NM_001042544.1:c.365del
NM_003573.2:c.254del
NP_001036009.1:p.Leu122fs
NP_003564.2:p.Leu85fs
NC_000019.9:g.41105997del
NC_000019.9:g.41105997delT
NM_003573.2:c.254delT
p.Leu85ArgfsX15

Protein change:

L122fs

Links:

dbSNP: rs747013505

NCBI 1000 Genomes Browser:

rs747013505

Molecular consequence:

NM_001042544.1:c.365del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003573.2:c.254del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies
Synonyms:: URBAN-RIFKIN-DAVIS SYNDROME; Cutis laxa with severe pulmonary, gastrointestinal, and urinary abnormalities; Cutis laxa, autosomal recessive, type IC
Identifiers:: MONDO: MONDO:0013170; MedGen: C2750804; Orphanet: 221145; OMIM: 613177

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000221197	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jan 17, 2014)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19836010, 22829427, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000221197

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jan 17, 2014)

germline

clinical testing

PubMed (3)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development.

Urban Z, Hucthagowder V, Schürmann N, Todorovic V, Zilberberg L, Choi J, Sens C, Brown CW, Clark RD, Holland KE, Marble M, Sakai LY, Dabovic B, Rifkin DB, Davis EC.

Am J Hum Genet. 2009 Nov;85(5):593-605. doi: 10.1016/j.ajhg.2009.09.013. Epub 2009 Oct 15.

PubMed [citation]

PMID:: 19836010
PMCID:: PMC2775835

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Callewaert B, Su CT, Van Damme T, Vlummens P, Malfait F, Vanakker O, Schulz B, Mac Neal M, Davis EC, Lee JG, Salhi A, Unger S, Heimdal K, De Almeida S, Kornak U, Gaspar H, Bresson JL, Prescott K, Gosendi ME, Mansour S, Piérard GE, Madan-Khetarpal S, et al.

Hum Mutat. 2013 Jan;34(1):111-21. doi: 10.1002/humu.22165. Epub 2012 Aug 13.

PubMed [citation]

PMID:: 22829427
PMCID:: PMC4105850

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq, SCV000221197.2

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

Description

The Leu85ArgfsX15 variant in LTBP4 has not been previously reported in individuals with autosomal recessive cutis laxa type I, but has been identified in 1/5840 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 85 and lead to a premature termination codon 15 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of LTBP4 function has previously been desribed in homozygous and compound heterozygous individuals with autosomal recessive cutis laxa type IC (Urban 2009, Callewaert 2013). In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive cutis laxa type IC (http://pcpgm.partners.org/LMM).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Dec 7, 2024

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