Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001348505 | SCV001542809 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2020-08-14 | criteria provided, single submitter | clinical testing | 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 serine with arginine at codon 2040 of the FLNA protein (p.Ser2040Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. 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. |
Prevention |
RCV004734138 | SCV005341736 | uncertain significance | FLNA-related disorder | 2024-09-12 | no assertion criteria provided | clinical testing | The FLNA c.6142A>C variant is predicted to result in the amino acid substitution p.Ser2048Arg. This variant has been reported as a variant of uncertain significance in a patient with intellectual disability and multiple congenital anomalies (Leite et al., 2022. PubMed ID: 35390071). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |