ClinVar Miner

Submissions for variant NM_147196.3(TMIE):c.251G>T (p.Arg84Leu)

dbSNP: rs397517866
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041230 SCV000064921 likely pathogenic Rare genetic deafness 2013-01-18 criteria provided, single submitter clinical testing The Arg84Leu variant in TMIE has not been reported in the literature nor previou sly identified by our laboratory. However, another pathogenic variant affecting the same amino acid (Arg84Trp) has been reported as a founder mutation in the Tu rkish population (Sirmaci 2009). The Arg84Leu variant has not been identified in large and broad populations by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS/). Computational analyses (biochemical amino acid propertie s, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg84Leu varia nt may impact the protein, though this information is not predictive enough to d etermine pathogenicity. In summary, the clinical significance of this variant ca nnot be determined with certainty; however, its occurrence at the same amino aci d position of another known pathogenic mutation and the presence of a second var iant in trans in this individual's son support a likely pathogenic role.

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