ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4084G>A (p.Gly1362Arg)

dbSNP: rs2148111460
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001550988 SCV001771403 uncertain significance not provided 2021-06-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Labcorp Genetics (formerly Invitae), Labcorp RCV001859370 SCV002239195 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2021-10-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1362 of the FLNA protein (p.Gly1362Arg). ClinVar contains an entry for this variant (Variation ID: 1190326). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 expected to disrupt FLNA protein function.
PreventionGenetics, part of Exact Sciences RCV004542000 SCV004800487 uncertain significance FLNA-related disorder 2024-02-16 no assertion criteria provided clinical testing The FLNA c.4084G>A variant is predicted to result in the amino acid substitution p.Gly1362Arg. This variant has been reported, hemizygous, in one fetus with bilateral severe hydronephrosis (Miceikaite et al. 2023. PubMed ID: 37355983). This variant is absent from large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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