ClinVar

Description

This variant is also known as c.4927G>A (p.Gly1643Ser). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly1612 amino acid residue in FLNB. Other variant(s) that disrupt this residue have been observed in individuals with FLNB-related conditions (PMID: 16752402), which suggests that this may be a clinically significant amino acid residue. 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 FLNB protein function. ClinVar contains an entry for this variant (Variation ID: 1490901). This missense change has been observed in individual(s) with clinical features of Larsen syndrome (PMID: 27048506; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1612 of the FLNB protein (p.Gly1612Ser).