Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001221672 | SCV001393732 | uncertain significance | Primary ciliary dyskinesia | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2057 of the DNAH11 protein (p.Leu2057Pro). This variant is present in population databases (rs777354329, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DNAH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 950053). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH11 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. |
| Ambry Genetics | RCV001221672 | SCV002655797 | uncertain significance | Primary ciliary dyskinesia | 2021-11-02 | criteria provided, single submitter | clinical testing | The p.L2057P variant (also known as c.6170T>C), located in coding exon 36 of the DNAH11 gene, results from a T to C substitution at nucleotide position 6170. The leucine at codon 2057 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |