ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.7802G>A (p.Cys2601Tyr) (rs1060500721)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475302 SCV000543690 uncertain significance Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 1 2016-10-09 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 2593 of the FLNA protein (p.Cys2593Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FLNA-related disease. 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507907 SCV000603746 uncertain significance not provided 2017-05-05 criteria provided, single submitter clinical testing The p.Cys2593Tyr variant has not been reported in the medical literature or gene specific variation databases but it has been reported to ClinVar (Variation ID: 405458). It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Exome Aggregation Consortium (ExAC) browser. The cysteine at position 2593 is highly conserved, up to Tetraodon (considering 10 species, Alamut v.2.9.0) and computational analyses of the effects of the p.Cys2593Tyr variant on protein structure and function predict a deleterious effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Cys2593Tyr variant with certainty.

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.