Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000603987 | SCV000710861 | likely pathogenic | Rare genetic deafness | 2016-05-02 | criteria provided, single submitter | clinical testing | The p.Ala411Pro variant in SLC26A4 has been reported in the compound heterozygou s state in two Latino siblings with Pendred syndrome (Trevino 2001). It has not been identified in large population studies. In addition, a different amino acid change at this position (p.Ala411Thr) has been reported in individuals with Pen dred syndrome (Courtmans 2007) further suggesting that a change at this location may not be tolerated. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional s tudies are required to fully establish its clinical significance, the p.Ala411Pr o variant is likely pathogenic. |
| Labcorp Genetics |
RCV001868006 | SCV002238485 | pathogenic | not provided | 2024-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 411 of the SLC26A4 protein (p.Ala411Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Pendred syndrome (PMID: 11375792; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 504511). 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 80%. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003471971 | SCV004201894 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-08-09 | criteria provided, single submitter | clinical testing |