Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000826039 | SCV000967530 | uncertain significance | not specified | 2019-02-14 | criteria provided, single submitter | clinical testing | The p.Thr307Met variant in SLC26A4 has been reported in one compound heterozygous individual with nonsyndromic hearing loss and EVA. However, a third variant in SLC26A4 was identified in cis with the p.Thr307Met variant in this patient (Albert 2006). The variant has also been reported in the heterozygous state in three individuals with nonsyndromic hearing loss ( Pera 2008, Du 2014), one of whom also carried a second variant in SLC26A4 in cis with this variant (Pera 2008). The p.Thr307Met has also been identified in 0.023% (7/30604) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3. |
Invitae | RCV002538240 | SCV003440206 | uncertain significance | not provided | 2022-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 307 of the SLC26A4 protein (p.Thr307Met). This variant is present in population databases (rs144691257, gnomAD 0.02%). This missense change has been observed in individual(s) with deafness (PMID: 16570074, 18285825, 25788563). ClinVar contains an entry for this variant (Variation ID: 667326). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ce |
RCV002538240 | SCV004155765 | likely pathogenic | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | SLC26A4: PM1, PM2, PM3, PM5 |