ClinVar Miner

Submissions for variant NM_000503.6(EYA1):c.679G>A (p.Ala227Thr)

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 RCV003037297 SCV003440891 uncertain significance Melnick-Fraser syndrome 2024-06-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 227 of the EYA1 protein (p.Ala227Thr). This variant is present in population databases (rs202168841, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with deafness or congenital anomalies of kidney and urinary tract (PMID: 34906515, 36597107). ClinVar contains an entry for this variant (Variation ID: 2136680). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EYA1 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.
GeneDx RCV004593144 SCV005079030 uncertain significance not provided 2023-11-29 criteria provided, single submitter clinical testing Identified in a patient with a conotruncal heart defect in published literature (PMID: 29043394); Identified in a patient with left renal agenesis and right hypoplastic kidney in published literature (PMID: 34906515); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29043394, 34906515)
Fulgent Genetics, Fulgent Genetics RCV005045182 SCV005679075 uncertain significance Branchiootic syndrome 1; Branchiootorenal syndrome 1; Otofaciocervical syndrome 1 2024-01-20 criteria provided, single submitter clinical testing

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.