Submissions for variant NM_001110556.2(FLNA):c.7436G>T (p.Cys2479Phe)

dbSNP: rs2067604638

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032677	SCV002216731	uncertain significance	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2021-02-09	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 not present in population databases (ExAC no frequency). This sequence change replaces cysteine with phenylalanine at codon 2471 of the FLNA protein (p.Cys2471Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723427	SCV001957921	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723427	SCV001967724	uncertain significance	not provided		no assertion criteria provided	clinical testing