ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1343C>T (p.Ser448Leu)

gnomAD frequency: 0.00002  dbSNP: rs747076316
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664579 SCV000788566 likely pathogenic Pendred syndrome 2017-04-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001061723 SCV001226476 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 448 of the SLC26A4 protein (p.Ser448Leu). This variant is present in population databases (rs747076316, gnomAD 0.01%). This missense change has been observed in individual(s) with SLC26A4-related diseases (PMID: 15933521, 17443271, 17697873, 18813951, 21557232, 21961810, 23965030, 24612839, 32447495). 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: 549979). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV000664579 SCV002556952 pathogenic Pendred syndrome 2022-02-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002499145 SCV002813564 pathogenic Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome 2024-05-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV003472064 SCV004201914 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2024-01-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000664579 SCV005202750 pathogenic Pendred syndrome 2024-07-10 criteria provided, single submitter clinical testing Variant summary: SLC26A4 c.1343C>T (p.Ser448Leu) 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. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2e-05 in 251068 control chromosomes. c.1343C>T has been reported in the literature in multiple individuals affected with Pendred Syndrome (examples: (Kahrizi_2015, Ideura_2019, Liu_2020).). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 18813951, 31427586, 32447495). ClinVar contains an entry for this variant (Variation ID: 549979). Based on the evidence outlined above, the variant was classified as pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV002499145 SCV005417783 pathogenic Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome criteria provided, single submitter clinical testing PM2_Supporting+PM3_VeryStrong+PP3
Natera, Inc. RCV000664579 SCV001459927 likely pathogenic Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.