ClinVar Miner

Submissions for variant NM_001256317.3(TMPRSS3):c.497G>T (p.Arg166Leu) (rs150397427)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154656 SCV000204332 likely benign not specified 2016-05-02 criteria provided, single submitter clinical testing p.Arg166Leu in Exon 6 of TMPRSS3: This variant is not expected to have clinical significance because it has been identified in 0.3% (19/6614) of Finnish chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs150397427).
Illumina Clinical Services Laboratory,Illumina RCV000270576 SCV000436170 uncertain significance Deafness, autosomal recessive 8 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000766545 SCV000577412 uncertain significance not provided 2017-03-30 criteria provided, single submitter clinical testing The R166L variant in the TMPRSS3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R166L variant is observed in 19/6614 (0.3%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The R166L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R166L as a variant of uncertain significance.

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