Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000169571 | SCV000840531 | pathogenic | Pendred syndrome | 2018-09-10 | reviewed by expert panel | curation | The p.Ile124Tyrfs variant in SLC26A4 is predicted to cause a premature stop codon in biologically-relevant-exon 4/21 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). The allele frequency of the p.Ile124fs variant is in 0.003% (1/30782) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2). At least one patient with the variant displayed features of enlarged vestibular aqueduct and Mondini malformation which are consistent with Pendred syndrome (PP4; PMID:15679828). This variant has been detected in 2 patients with hearing loss in trans with suspected pathogenic variants (PM3_P, PMID:15679828). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Pendred syndrome based on the ACMG/AMP criteria applied: PVS1, PM2, PP4, PM3_P. |
Counsyl | RCV000169571 | SCV000221071 | likely pathogenic | Pendred syndrome | 2015-01-22 | criteria provided, single submitter | literature only | |
Ce |
RCV000488403 | SCV000575531 | likely pathogenic | not provided | 2016-09-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000488403 | SCV000947141 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile124Tyrfs*58) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). This variant is present in population databases (rs773738163, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with enlarged vestibular aqueduct (PMID: 15679828, 24051746). ClinVar contains an entry for this variant (Variation ID: 189148). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003474916 | SCV004201913 | pathogenic | Autosomal recessive nonsyndromic hearing loss 4 | 2023-06-13 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000169571 | SCV001455795 | pathogenic | Pendred syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |