Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV005037820 | SCV005667029 | uncertain significance | Autosomal dominant palmoplantar keratoderma and congenital alopecia; Craniometaphyseal dysplasia, autosomal recessive; Oculodentodigital dysplasia, autosomal recessive; Syndactyly type 3; Oculodentodigital dysplasia; Erythrokeratodermia variabilis et progressiva 3 | 2024-02-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005105256 | SCV005831712 | uncertain significance | Oculodentodigital dysplasia, autosomal recessive | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 102 of the GJA1 protein (p.Lys102Met). This variant is present in population databases (rs777767461, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GJA1-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GJA1 protein function with a negative predictive value of 80%. This variant disrupts the p.Lys102 amino acid residue in GJA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19338053). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |