Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673239 | SCV000798420 | uncertain significance | Pendred syndrome | 2018-03-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673239 | SCV004020618 | likely pathogenic | Pendred syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A4 c.1589A>C (p.Tyr530Ser) results in a non-conservative amino acid change in 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 8e-06 in 251192 control chromosomes. c.1589A>C has been reported in the literature in multiple individuals affected with SLC26A4-related conditions (e.g., Pryor_2005, Banghova_2008, Porova_2010). In at least two individuals the variant was identified in compound heterozygosity with other known pathogenic variants. These data indicate that the variant is likely associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, demonstrating that the variant protein product displays abnormal trafficking activity and is largely retained in the endoplasmic reticulum. Additionally, other variants at the Tyr530 residue have been reported as associated with disease (p.Tyr530His), suggesting that this codon is functionally important. The following publications have been ascertained in the context of this evaluation (PMID: 19189692, 19204907, 20597900, 15689455). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003472153 | SCV004201945 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-04-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004719936 | SCV005324854 | likely pathogenic | not provided | 2023-04-21 | criteria provided, single submitter | clinical testing | Identified in a patient with enlargement of the vestibular aqueduct without thyroid dysfunction; patient also had a pathogenic SLC26A4 variant on the other allele (Pryor et al., 2005); Published functional studies suggest a damaging effect on protein localization and function (Choi et al., 2009); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19204907, 15689455) |