Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469306 | SCV002766035 | pathogenic | Pendred syndrome | 2024-08-15 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A4 c.367C>T (p.Pro123Ser) results in a non-conservative amino acid change located in the SLC26A/SulP transporter domain (IPR011547) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251418 control chromosomes.c.367C>T has been reported in the literature in homozygous- and compound heterozygous individuals affected with nonsyndromic hearing loss and Pendred Syndrome (Tsukamoto_2003, Miyagawa_2014, Ideura_2019, Nakano_2022, Reis_2022). These data indicate that the variant is likely to be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated decreased membrane localization and almost complete absence of transporter activity for the variant protein (Ishihara_2010, Wasano_2020). The following publications have been ascertained in the context of this evaluation (PMID: 31427586, 20826203, 24599119, 34801268, 35580552, 14508505, 31599023). ClinVar contains an entry for this variant (Variation ID: 691506). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001004620 | SCV004201832 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-11-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003558616 | SCV004294535 | pathogenic | not provided | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 123 of the SLC26A4 protein (p.Pro123Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 24599119, 31427586). ClinVar contains an entry for this variant (Variation ID: 691506). 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: 20826203, 31599023, 32165640). For these reasons, this variant has been classified as Pathogenic. |
| National Institute of Sensory Organs, |
RCV001004620 | SCV000994864 | affects | Autosomal recessive nonsyndromic hearing loss 4 | 2019-08-20 | no assertion criteria provided | clinical testing | in vitro experiment |