ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.1804A>G (p.Ile602Val)

dbSNP: rs1057522788
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434400 SCV000529480 uncertain significance not provided 2016-06-29 criteria provided, single submitter clinical testing The I602V variant in the FLNA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I602V variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I602V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I602V as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861587 SCV002118993 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2021-06-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 602 of the FLNA protein (p.Ile602Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. 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: 387435). This variant is not present in population databases (ExAC no frequency).

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