Submissions for variant NM_206933.4(USH2A):c.632G>A (p.Trp211Ter)

dbSNP: rs727504893

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156272	SCV000205989	pathogenic	Rare genetic deafness	2013-12-23	criteria provided, single submitter	clinical testing	The Trp211X variant in USH2A has not been previously reported in individuals wit h hearing loss or in large population studies. This nonsense variant leads to a premature termination codon at position 211, which is predicted to lead to a tru ncated or absent protein. In summary, this variant meets our criteria to be clas sified as pathogenic (http://pcpgm.partners.org/LMM).
Baylor Genetics	RCV003462062	SCV004207719	pathogenic	Retinitis pigmentosa 39	2023-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479025	SCV004222874	pathogenic	Usher syndrome	2023-11-17	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.632G>A (p.Trp211X) results in a premature termination codon and is predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 250800 control chromosomes (gnomAD). To our knowledge, no occurrence of c.632G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, another variant resulting in the same amino acid change, c.633G>A (p.Trp211X) has been reported in the literature in at least one individual affected with Usher Syndrome (e.g. Bonnet_2016, PMID: 27460420). No submitters have cited clinical-significance assessments for c.632G>A to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.