Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002267100 | SCV002549619 | pathogenic | not provided | 2022-01-20 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate defective protease activity of the variant protein compared to wild-type (Lee et al., 2003), and failure to undergo proteolytic cleavage and activate the epithelial sodium channel (ENaC) in vitro (Guipponi et al., 2002); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15447792, 12393794, 12920079, 11424922, 32842620, 21534946, 11907649) |
Fulgent Genetics, |
RCV002486095 | SCV002794461 | pathogenic | Autosomal recessive nonsyndromic hearing loss 8 | 2022-02-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002267100 | SCV004297388 | pathogenic | not provided | 2023-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 407 of the TMPRSS3 protein (p.Cys407Arg). This variant is present in population databases (rs773780151, gnomAD 0.03%). This missense change has been observed in individuals with hearing loss (PMID: 11424922). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 996724). 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 TMPRSS3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects TMPRSS3 function (PMID: 12920079). For these reasons, this variant has been classified as Pathogenic. |
University of Washington Center for Mendelian Genomics, |
RCV001291489 | SCV001479993 | likely pathogenic | Hearing loss, autosomal recessive | no assertion criteria provided | research |