NM_000358.3(TGFBI):c.370C>T (p.Arg124Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002512901.4

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439201	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 4, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9054935, 9463327, 10798644, 11923233, 23559853, 28492532
SCV005078734	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 8, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439201

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 4, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV005078734

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 8, 2024)

germline

clinical testing

Citation Link

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Mutation hot spots in 5q31-linked corneal dystrophies.

Korvatska E, Munier FL, Djemaï A, Wang MX, Frueh B, Chiou AG, Uffer S, Ballestrazzi E, Braunstein RE, Forster RK, Culbertson WW, Boman H, Zografos L, Schorderet DF.

Am J Hum Genet. 1998 Feb;62(2):320-4.

PubMed [citation]

PMID:: 9463327
PMCID:: PMC1376896

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439201.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 124 of the TGFBI protein (p.Arg124Cys). This variant is present in population databases (rs121909210, gnomAD 0.004%). This missense change has been observed in individuals with autosomal dominant corneal dystrophy (PMID: 9054935, 9463327, 10798644, 11923233). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7868). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TGFBI function (PMID: 23559853). 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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005078734.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16380889, 15302666, 19337156, 20458218, 25055147, 22850414, 21135107, 23559853, 25785536, 9054935, 27348782, 15013897, 28393022, 16710170, 18615206, 29085627, 28358433, 20697279, 22746317, 11923233, 22355247, 20360992, 20161820, 20806046, 34426522, 16118514, 33816482, 35985662, 28689406, 12770961, 18470323, 30805211, 30098247, 12586172, 20664689)

#	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

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