Total submissions: 6
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- |
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, |
RCV000785622 | SCV000994861 | affects | Autosomal recessive nonsyndromic hearing loss 4 | 2019-08-20 | no assertion criteria provided | clinical testing | in vitro experiment |