Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory; Baylor College of Medicine | RCV000119811 | SCV000154737 | unknown | Autosomal recessive nonsyndromic hearing loss 4 | criteria provided, single submitter | not provided | Converted during submission to Uncertain significance. | |
| Invitae | RCV002515809 | SCV003440084 | likely pathogenic | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 231 of the SLC26A4 protein (p.Val231Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Pendred syndrome (PMID: 25991456). ClinVar contains an entry for this variant (Variation ID: 133300). 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 expected to disrupt SLC26A4 protein function with a positive predictive value of 95%. This variant disrupts the p.Val231 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC26A4-related conditions (PMID: 19287372, 25372295, 25991456), 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. |