Submissions for variant NM_000358.3(TGFBI):c.1664G>A (p.Arg555Gln)

dbSNP: rs121909209

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetics and Molecular Pathology, SA Pathology	RCV000008316	SCV001981652	pathogenic	Thiel-Behnke corneal dystrophy	2021-09-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002512900	SCV003439285	pathogenic	not provided	2025-01-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 555 of the TGFBI protein (p.Arg555Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant corneal dystrophy (PMID: 22355247). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7867). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TGFBI protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects TGFBI function (PMID: 21135107). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV002512900	SCV004704306	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TGFBI: PS2, PM2, PM5, PS4:Moderate, PP1, PS3:Supporting, BP4
OMIM	RCV000008316	SCV000028524	pathogenic	Thiel-Behnke corneal dystrophy	2012-01-01	no assertion criteria provided	literature only