Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756762 | SCV000884668 | likely pathogenic | not provided | 2017-11-09 | criteria provided, single submitter | clinical testing | The p.Arg1890Cys variant (rs121909063) has been shown segregating with sensorineural hearing loss across four families including Dutch, American and two Spanish (Plantinga, 2006 and Hildebrand, 2011). All affected individuals display middle frequencies impairment indicated by a trough-shaped profile in the audiogram. This variant occurs in the ZP domain of TECTA, a region of the polypeptide required for polymerization into high molecular weight filaments where it is incorporated into the extracellular matrix (Jovine, 2002). This variant is listed in the Genome Aggregation Database (gnomAD) identified on a single chromosome out of 246,248, and has been reported to the ClinVar database as a pathogenic variant (Variation ID: 7022). The arginine at position 1890 is highly conserved considering 11 species (Alamut v2.10) and computational analyses of the p.Arg1890Cys variant on protein structure and function indicate a deleterious effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: probably damaging). Given the current evidence, the p.Arg1890Cys is likely to be pathogenic. |
| INGEBI, |
RCV001544521 | SCV001763594 | pathogenic | Nonsyndromic genetic hearing loss | 2021-07-15 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: The c.5688C>T variant in TECTA gene is absent from population databases applying to PM2 criteria. This variant has been detected in two different probands meeting PS4_ Supporing (PMID: 16718611 and this study). This change segregated in eleven affected memebers in a family and 4 affected memebrs in another family, both with non-syndromic hearing loss which meets the PP1_VeryStrong criteria (PMID: 16718611 and this study). Revel score was 0.503 not apllying neither PM3 nor BP4. Consider all the evidene (PM2, PP1_Strong and PS4_Supp) the variant is classified as Pathogenic for autosomal dominant non-syndromic hearing loss |
| Gene |
RCV000756762 | SCV001874728 | pathogenic | not provided | 2022-03-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18022253, 24636747, 18776598, 17136632, 28946916, 16718611, 31554319, 33297549, 27535533, 21520338, 9590290, 30935366) |
| Labcorp Genetics |
RCV000756762 | SCV003440426 | pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1890 of the TECTA protein (p.Arg1890Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant deafness (PMID: 16718611, 21520338, 28946916, 30935366, 31554319, 33297549, 34795337). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7022). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TECTA protein function. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000007437 | SCV000027637 | pathogenic | Autosomal dominant nonsyndromic hearing loss 12 | 2006-06-01 | no assertion criteria provided | literature only |