rs782549299

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21520333)

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 413 of the FLNA protein (p.Thr413Met). This variant is present in population databases (rs782549299, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of FLNA-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 211010). 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. 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.

The p.T413M variant (also known as c.1238C>T), located in coding exon 8 of the FLNA gene, results from a C to T substitution at nucleotide position 1238. The threonine at codon 413 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.