ClinVar Miner

Submissions for variant NM_001256317.3(TMPRSS3):c.595G>A (p.Val199Met)

gnomAD frequency: 0.00004  dbSNP: rs772040483
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome-Nilou Lab RCV001509549 SCV001712136 likely pathogenic Autosomal recessive nonsyndromic hearing loss 8 2021-06-09 criteria provided, single submitter clinical testing found in a 38-year-old male with prelingual deafness at homozygous state.
GeneDx RCV001724324 SCV001986277 uncertain significance not provided 2020-11-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21786053, 28695016, 25474651, 28246597)
Invitae RCV001724324 SCV004297399 pathogenic not provided 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 199 of the TMPRSS3 protein (p.Val199Met). This variant is present in population databases (rs772040483, gnomAD 0.008%). This missense change has been observed in individual(s) with deafness (PMID: 21786053). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1164000). 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 TMPRSS3 protein function. For these reasons, this variant has been classified as Pathogenic.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001724324 SCV001955922 likely pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001724324 SCV001970065 pathogenic not provided no assertion criteria provided clinical testing

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