Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002376037 | SCV002685545 | uncertain significance | Primary ciliary dyskinesia | 2016-12-12 | criteria provided, single submitter | clinical testing | The p.I30V variant (also known as c.88A>G), located in coding exon 1 of the SPAG1 gene, results from an A to G substitution at nucleotide position 88. The isoleucine at codon 30 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other 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. |
| Labcorp Genetics |
RCV003100053 | SCV003250777 | uncertain significance | Primary ciliary dyskinesia 28 | 2025-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 30 of the SPAG1 protein (p.Ile30Val). This variant is present in population databases (rs550123264, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1765028). 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 SPAG1 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002376037 | SCV003682271 | uncertain significance | Primary ciliary dyskinesia | 2021-06-22 | criteria provided, single submitter | clinical testing | The c.88A>G (p.I30V) alteration is located in exon 2 (coding exon 1) of the SPAG1 gene. This alteration results from a A to G substitution at nucleotide position 88, causing the isoleucine (I) at amino acid position 30 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |