NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys) AND Lattice corneal dystrophy Type I

Germline classification:: Pathogenic (2 submissions)
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:: RCV000008317.10

Allele description [Variation Report for NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys)]

NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys)

Gene:

TGFBI:transforming growth factor beta induced [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys)

HGVS:

NC_000005.10:g.136046406C>T
NG_012646.1:g.22512C>T
NM_000358.3:c.370C>TMANE SELECT
NP_000349.1:p.Arg124Cys
NC_000005.9:g.135382095C>T
NM_000358.2:c.370C>T
Q15582:p.Arg124Cys

Protein change:

R124C; ARG124CYS

Links:

UniProtKB: Q15582#VAR_005076; OMIM: 601692.0003; dbSNP: rs121909210

NCBI 1000 Genomes Browser:

rs121909210

Molecular consequence:

NM_000358.3:c.370C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lattice corneal dystrophy Type I (CDL1)
Synonyms:: Lattice corneal dystrophy type 1
Identifiers:: MONDO: MONDO:0007380; MedGen: C1690006; Orphanet: 98964; OMIM: 122200

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
SCV000028525	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9054935, 9559741
SCV004171829	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028525

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 1998)

germline

literature only

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

SCV004171829

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.

Munier FL, Korvatska E, Djemaï A, Le Paslier D, Zografos L, Pescia G, Schorderet DF.

Nat Genet. 1997 Mar;15(3):247-51.

PubMed [citation]

PMID:: 9054935

Lattice corneal dystrophy type 1 in a Canadian kindred is associated with the Arg124 --> Cys mutation in the kerato-epithelin gene. sgupta@ogh.on.ca.

Gupta SK, Hodge WG, Damji KF, Guernsey DL, Neumann PE.

Am J Ophthalmol. 1998 Apr;125(4):547-9.

PubMed [citation]

PMID:: 9559741

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000028525.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 2 families with lattice corneal dystrophy type I (CDL1; 122200), Munier et al. (1997) found an arg124-to-cys (R124C) mutation in the TGFBI gene due to change in a CpG dinucleotide. The diseases resulting from mutations in codon 124 (see also 601692.0004) were accompanied by amyloid deposits, suggesting that the R124-mutated keratoepithelin forms amyloidogenic intermediates that precipitate in the cornea.

The same C-to-T mutation at position 417 in exon 4 of the TGFBI gene was described in a Canadian kindred with lattice corneal dystrophy type I by Gupta et al. (1998). No genealogic connection of this family with the 2 previously studied Swiss families was known.

#	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		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004171829.1

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

Description

The missense c.370C>T (p.Arg124Cys) variant in TGFBI gene has been reported in individuals affected with Corneal dystrophy (Grothe HL et al. 2013). It has also been observed to segregate with disease in related individuals. The p.Arg124Cys variant has allele frequency 0.0007% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submitter). The amino acid Arg at position 124 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine