ClinVar Miner

Submissions for variant NM_012186.3(FOXE3):c.334C>T (p.Pro112Ser)

gnomAD frequency: 0.00004  dbSNP: rs745571457
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001062207 SCV001226989 uncertain significance Congenital primary aphakia; Anterior segment dysgenesis 2023-02-18 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 112 of the FOXE3 protein (p.Pro112Ser). This variant is present in population databases (rs745571457, gnomAD 0.008%). This missense change has been observed in individual(s) with thoracic aortic disease (PMID: 26854927). ClinVar contains an entry for this variant (Variation ID: 617853). 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 FOXE3 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.
Ambry Genetics RCV002325454 SCV002607128 uncertain significance Cardiovascular phenotype 2020-02-19 criteria provided, single submitter clinical testing The p.P112S variant (also known as c.334C>T), located in coding exon 1 of the FOXE3 gene, results from a C to T substitution at nucleotide position 334. The proline at codon 112 is replaced by serine, an amino acid with similar properties. This variant has been detected in a thoracic aortic aneurysm and dissection cohort; however, details were limited (Kuang SQ et al. J. Clin. Invest., 2016 Mar;126:948-61). This amino acid position is not conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Center for Mendelian Genomics, University of Washington RCV000755153 SCV000882975 likely benign Congenital aneurysm of ascending aorta; Acute aortic dissection 2016-02-08 no assertion criteria provided research
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001703236 SCV001930156 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001703236 SCV001972928 likely benign not provided no assertion criteria provided clinical testing

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