ClinVar Miner

Submissions for variant NM_001256317.3(TMPRSS3):c.412G>A (p.Ala138Thr) (rs140614903)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039355 SCV000063039 uncertain significance not specified 2016-02-02 criteria provided, single submitter clinical testing The p.Ala138Thr variant in TMPRSS3 has now been identified by our laboratory in three individuals with hearing loss, but a variant affecting the remaining copy of the TMPRSS3 gene has not been identified in any of them. This variant has bee n identified in 0.06% (71/121400) of chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs140614903); however, its fre quency is not high enough to rule out a pathogenic role. This variant occurs at the same position as a different amino acid change, p.Ala138Glu, reported in a h omozygous state in an affected sib-pair (Hutchin 2005) and identified by our lab oratory in four individuals, three of whom have a second pathogenic or likely pa thogenic variant. This increases the likelihood of pathogenicity for the p.Ala13 8Thr variant. However, the alanine to threonine change is a more conservative ch ange than alanine to glutamic acid. Computational prediction tools and conservat ion analyses do not provide strong support for or against an impact to the prote in. In summary, the clinical significance of the p.Ala138Thr variant is uncertai n.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000730846 SCV000858611 uncertain significance not provided 2017-12-21 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000730846 SCV001448956 uncertain significance not provided 2019-10-16 criteria provided, single submitter clinical testing
Department of Otolaryngology – Head & Neck Surgery,Cochlear Implant Center RCV001375064 SCV001571833 uncertain significance Waardenburg syndrome 2021-04-12 criteria provided, single submitter clinical testing PM2_Moderate, PM5_Moderate, BP4_Supporting

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