ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4366C>T (p.Pro1456Ser)

dbSNP: rs1557177405
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521370 SCV000620465 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FLNA gene. The P1456S variant has not been published as pathogenic or been reported as benign to our knowledge. The P1456S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1456S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved.
Labcorp Genetics (formerly Invitae), Labcorp RCV005222995 SCV005865807 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-09-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1456 of the FLNA protein (p.Pro1456Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 451728). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FLNA protein function with a negative predictive value of 95%. 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.

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