Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000824321 | SCV000965215 | likely pathogenic | Primary ciliary dyskinesia | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3429 of the DNAH11 protein (p.Arg3429His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 665934). 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. This variant disrupts the p.Arg3429 amino acid residue in DNAH11. Other variant(s) that disrupt this residue have been observed in individuals with DNAH11-related conditions (PMID: 26139845), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |