Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000320959 | SCV000329521 | pathogenic | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect; L90P interferes with proper localization of the SLC26A4 protein (Choi et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26969326, 15689455, 19204907, 25394566, 19318451, 23555729) |
ARUP Laboratories, |
RCV000507599 | SCV000605151 | pathogenic | not specified | 2017-03-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000320959 | SCV001225432 | pathogenic | not provided | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 514 of the SLC26A4 protein (p.Gln514Arg). This variant is present in population databases (rs111033316, gnomAD 0.01%). This missense change has been observed in individuals with Pendred syndrome (PMID: 15689455, 25394566, 26969326). ClinVar contains an entry for this variant (Variation ID: 43511). 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%. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 19204907). This variant disrupts the p.Gln514 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18285825, 19017801). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000666548 | SCV002026938 | pathogenic | Pendred syndrome | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003473266 | SCV004201841 | pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-10-14 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000036445 | SCV000060100 | likely pathogenic | Rare genetic deafness | 2009-06-03 | no assertion criteria provided | clinical testing | |
Counsyl | RCV000666548 | SCV000790855 | likely pathogenic | Pendred syndrome | 2017-04-12 | no assertion criteria provided | clinical testing |