Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664842 | SCV000788860 | likely pathogenic | Pendred syndrome | 2016-12-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855431 | SCV002241394 | pathogenic | not provided | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 457 of the SLC26A4 protein (p.Asn457Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Pendred syndrome and deafness (PMID: 12676893, 20597900). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550172). 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. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 31599023). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001004642 | SCV004201845 | pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-10-11 | criteria provided, single submitter | clinical testing | |
| National Institute of Sensory Organs, |
RCV001004642 | SCV000994892 | affects | Autosomal recessive nonsyndromic hearing loss 4 | 2019-08-20 | no assertion criteria provided | literature only | in vitro experiment |