Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003764561 | SCV004571493 | pathogenic | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2023-04-07 | criteria provided, single submitter | clinical testing | Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on FLNA function (PMID: 30224736). For these reasons, this variant has been classified as Pathogenic. 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 sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 82 of the FLNA protein (p.Glu82Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with periventricular heterotopia (PMID: 11914408; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11754). |
OMIM | RCV000012520 | SCV000032754 | pathogenic | Heterotopia, periventricular, X-linked dominant | 2002-03-26 | no assertion criteria provided | literature only |