Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002017038 | SCV002302157 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2021-06-08 | 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 expected to disrupt FLNA protein function. This variant has been observed in individual(s) with X-linked otopalatodigital spectrum disorders (PMID: 26404489). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 229 of the FLNA protein (p.Met229Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |