ClinVar Miner

Submissions for variant NM_001256317.3(TMPRSS3):c.1360T>C (p.Ter454Arg)

gnomAD frequency: 0.00098  dbSNP: rs149919890
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001538548 SCV001756215 uncertain significance not provided 2021-08-18 criteria provided, single submitter clinical testing Normal stop codon changed to a Arg codon, leading to the addition of 9 amino acids at the C-terminus; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317480 SCV004021199 uncertain significance not specified 2023-06-20 criteria provided, single submitter clinical testing Variant summary: TMPRSS3 c.1363T>C (p.X455ArgextX9) changes the termination codon and is predicted to lead to an extended protein with an additional 9 amino acids added to the normal C-terminus. The variant allele was found at a frequency of 0.00018 in 251494 control chromosomes (gnomAD). c.1363T>C has been reported in the literature in a homozygous individual affected with severe to profound hearing loss (Adeyemo_2022). This report does not provide unequivocal conclusions about association of the variant with Deafness, Autosomal Recessive 8. Co-occurrence with another (likely) pathogenic variant was reported in the afforementioned individual in a homozygous state (TMPRSS3 c.323-6G>A), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34837038). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001538548 SCV004267804 likely benign not provided 2024-11-12 criteria provided, single submitter clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV003992500 SCV004810384 uncertain significance Autosomal recessive nonsyndromic hearing loss 8 2024-04-04 criteria provided, single submitter clinical testing

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