ClinVar Miner

Submissions for variant NM_000358.3(TGFBI):c.1501C>A (p.Pro501Thr)

dbSNP: rs121909212
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779458 SCV000916086 likely pathogenic Corneal dystrophy 2017-04-28 criteria provided, single submitter clinical testing The TGFBI c.1501C>A (p.Pro501Thr) missense variant has been reported in a heterozygous state in a total of 21 individuals with lattice corneal dystrophy type IIIA, a late-onset condition which manifests after the seventh decade of life (Yamamoto et al. 1998; Tsujikawa et al. 2002; Yu et al. 2006; Long et al. 2011; Kojima et al. 2013). Nine of these individuals were from three families (Yamamoto et al. 1998). The p.Pro501Thr variant is described as a founder variant in the Japanese and Chinese populations (Tsujikawa et al. 2002; Yu et al. 2006). This variant was also detected in a heterozygous state in three additional individuals, two with Fuchs endothelial corneal dystrophy and one with Thiel-Behnke corneal dystrophy (Chae et al. 2016). The p.Pro501Thr variant was also present in five unaffected individuals in a heterozygous state, which the authors suggest may be attributed to the late-onset of the disease or due to reduced penetrance (Ha et al. 2000; Chae et al. 2016). The p.Pro501Thr variant was absent from six unaffected family members and at least 150 control individuals (Yamamoto et al. 1998; Tsujikawa et al. 2002), but is reported at a frequency of 0.00404 in the East Asian population of the Exome Aggregation Consortium. In addition, there is one individual with the variant in a homozygous state in the Genome Aggregation Database. Based on collective evidence, the p.Pro501Thr variant is classified as likely pathogenic for autosomal dominant corneal dystrophy.
Invitae RCV001851732 SCV002255941 likely pathogenic not provided 2021-09-30 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 501 of the TGFBI protein (p.Pro501Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs121909212, ExAC 0.4%). This variant has been observed in individual(s) with lattice corneal dystrophy type IIIA, often with very late onset (PMID: 9497262, 10832717, 11024425, 21462384, 23884333). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7871). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV002247265 SCV002516085 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV000008320 SCV000028528 pathogenic Corneal dystrophy, lattice type 3A 2002-11-15 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.