Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826187 | SCV000967730 | likely pathogenic | Rare genetic deafness | 2019-03-06 | criteria provided, single submitter | clinical testing | The p.Cys1898Arg variant in TECTA has been reported in 1 individual with postlingual mid-frequency hearing loss and an autosomal dominant family history of hearing loss; however, no segregation evidence was available (Hildebrand 2011). Additionally, this variant was reported in 1 patient with hearing loss by our laboratory and segregated with disease in 5 affected relatives (including 2 obligate carriers). This variant was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Cys1898Arg variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hearing loss. ACMG/AMP criteria applied: PM2, PP1_Moderate, PP3, PS4_Supporting. |
| Labcorp Genetics |
RCV002538245 | SCV003440960 | uncertain significance | not provided | 2022-06-18 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 667414). This missense change has been observed in individual(s) with clinical features of autosomal dominant TECTA-related conditions. (PMID: 21520338). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1898 of the TECTA protein (p.Cys1898Arg). |