ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.3925G>A (p.Val1309Ile)

gnomAD frequency: 0.00001  dbSNP: rs782412141
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
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659666 SCV000781509 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001307125 SCV001496523 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2020-09-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1309 of the FLNA protein (p.Val1309Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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. 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 FLNA protein function. This variant has not been reported in the literature in individuals with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 547384). This variant is present in population databases (rs782412141, ExAC 0.002%).
Ambry Genetics RCV002369782 SCV002623746 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-11-29 criteria provided, single submitter clinical testing The p.V1309I variant (also known as c.3925G>A), located in coding exon 22 of the FLNA gene, results from a G to A substitution at nucleotide position 3925. The valine at codon 1309 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. 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.

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.