ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4069C>T (p.Arg1357Trp)

gnomAD frequency: 0.00001  dbSNP: rs373073505
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 RCV001889918 SCV002139588 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2021-04-09 criteria provided, single submitter clinical testing 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. This variant is present in population databases (rs373073505, ExAC 0.002%). This sequence change replaces arginine with tryptophan at codon 1357 of the FLNA protein (p.Arg1357Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226500 SCV003922842 uncertain significance not specified 2023-03-29 criteria provided, single submitter clinical testing Variant summary: FLNA c.4069C>T (p.Arg1357Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 180566 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4069C>T in individuals affected with Periventricular Nodular Heterotopia 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV004779166 SCV005388295 uncertain significance not provided 2024-03-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

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.