ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.511G>A (p.Ala171Thr) (rs201004645)

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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 RCV000037862 SCV000061524 uncertain significance not specified 2016-06-23 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala171Thr var iant in GJB2 has been previously reported in nine individuals with sensorineural hearing loss (Lin 2001, Najmabadi 2002, Wu 2002, Xiao 2004, Azaiez 2004, Putcha 2007, Samanich 2007, Han 2008, Bonyadi 2009, Bonyadi 2014, LMM data). However, a variant affecting the remaining copy of GJB2 was not identified in any of them . In addition, two individuals had cochlear malformations inconsistent with GJB 2-related hearing loss (Lin 2001, Wu 2002). One publication suggested that p.Ala 171Thr could be inherited in a dominant pattern (Xiao 2004); however, this is in consistent with findings from other studies. This variant has been identified i n two individuals with normal hearing (Samanich 2007, Han 2008) and has been ide ntified in 8/66556 European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs201004645). Computational prediction tools and conservation analysis suggest that the p.Ala171Thr variant may not imp act the protein, though this information is not predictive enough to rule out pa thogenicity. In summary, while the clinical significance of the p.Ala171Thr vari ant is uncertain, these data suggest that it is more likely to be benign.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000505525 SCV000599757 uncertain significance Deafness, autosomal recessive 1A 2017-05-09 criteria provided, single submitter clinical testing
Counsyl RCV000505525 SCV000795427 uncertain significance Deafness, autosomal recessive 1A 2017-11-14 criteria provided, single submitter clinical testing

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