Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218493 | SCV001390375 | uncertain significance | Familial aplasia of the vermis; Orofaciodigital syndrome I | 2023-03-24 | 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 OFD1 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 947419). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. This variant is present in population databases (rs761915805, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 747 of the OFD1 protein (p.Glu747Lys). |
Ambry Genetics | RCV002429931 | SCV002727940 | uncertain significance | Primary ciliary dyskinesia; Inborn genetic diseases | 2018-01-19 | criteria provided, single submitter | clinical testing | The p.E747K variant (also known as c.2239G>A), located in coding exon 16 of the OFD1 gene, results from a G to A substitution at nucleotide position 2239. The glutamic acid at codon 747 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |