ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.3395C>A (p.Pro1132His)

gnomAD frequency: 0.00007  dbSNP: rs893516153
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001925064 SCV002169585 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 1132 of the COL4A3 protein (p.Pro1132His). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL4A3-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL4A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002503542 SCV002784499 uncertain significance Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria 2022-04-19 criteria provided, single submitter clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis RCV004558720 SCV005047119 uncertain significance Alport syndrome 3b, autosomal recessive 2024-04-19 criteria provided, single submitter clinical testing The COL4A3 c.3395C>A (p.Pro1132His) variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters (ClinVar ID: 1402223) and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on COL4A3 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the COL4A3 c.3395C>A (p.Pro1132His) variant is uncertain at this time.

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.