Submissions for variant NM_001110556.2(FLNA):c.7798C>A (p.Pro2600Thr)

gnomAD frequency: 0.00001  dbSNP: rs377322094

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001902973	SCV002158591	uncertain significance	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2021-05-19	criteria provided, single submitter	clinical testing	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. This variant is present in population databases (rs377322094, ExAC 0.002%). This sequence change replaces proline with threonine at codon 2592 of the FLNA protein (p.Pro2592Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine.