Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000506390 | SCV000605390 | uncertain significance | not specified | 2017-04-10 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000506390 | SCV000710863 | uncertain significance | not specified | 2019-01-04 | criteria provided, single submitter | clinical testing | The p.Gly94Arg variant in TMPRSS3 has been reported in at least 2 individuals wi th hearing loss (Miyagawa 2013, LMM data). It has also been identified in 0.03% (42/129164) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID: 440339). Computational predicti on tools and conservation analysis suggest that the p.Gly94Arg variant may impac t the protein, though this information is not predictive enough to determine pat hogenicity. In summary, the clinical significance of the p.Gly94Arg variant is u ncertain. ACMG/AMP criteria applied: PM2_Supporting, PP3. |
Illumina Laboratory Services, |
RCV001140697 | SCV001300980 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 8 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Fulgent Genetics, |
RCV001140697 | SCV002786083 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 8 | 2021-09-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002524927 | SCV003482999 | uncertain significance | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 94 of the TMPRSS3 protein (p.Gly94Arg). This variant is present in population databases (rs143762350, gnomAD 0.03%). This missense change has been observed in individual(s) with hearing loss (PMID: 23967202, 25770132). ClinVar contains an entry for this variant (Variation ID: 440339). 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. 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. |