ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.269C>T (p.Ser90Leu)

dbSNP: rs370588279
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169192 SCV000220439 likely pathogenic Pendred syndrome 2014-06-20 criteria provided, single submitter literature only
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV000785622 SCV000924203 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 criteria provided, single submitter research
3billion RCV000785622 SCV002058680 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2022-01-03 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000188842, PMID:12676893, PS1_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.892, 3CNET: 0.971, PP3_P). A missense variant is a common mechanism associated with Deafness (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000020, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV001850391 SCV002278324 pathogenic not provided 2023-10-29 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 90 of the SLC26A4 protein (p.Ser90Leu). This variant is present in population databases (rs370588279, gnomAD 0.01%). This missense change has been observed in individuals with pre-lingual deafness or nonsyndromic enlargement of vestibular aqueduct (PMID: 12676893, 17443271, 20842945, 25372295, 27247933, 27792752, 32681043; Invitae). ClinVar contains an entry for this variant (Variation ID: 188842). 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: 32417962). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000785622 SCV004201852 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2023-09-28 criteria provided, single submitter clinical testing
National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center RCV000785622 SCV000994861 affects Autosomal recessive nonsyndromic hearing loss 4 2019-08-20 no assertion criteria provided clinical testing in vitro experiment

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