Submissions for variant NM_206933.4(USH2A):c.12700A>C (p.Thr4234Pro)

dbSNP: rs577938494

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376369	SCV001573486	uncertain significance	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.12700A>C variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221320	SCV000271290	likely pathogenic	Usher syndrome; Rare genetic deafness	2015-11-07	flagged submission	clinical testing	The p.Thr4234Pro variant in USH2A has been reported as a homozygous variant in o ne individual with clinical features of Usher syndrome type 2 (Lenarduzzi 2015), and was absent from large race-matched population studies. Computational predic tion tools and conservation analyses of the predicted amino acid change at this position do not provide strong support for or against an impact to the protein. However, the nucleotide base affected by the variant (the adenosine (A) base at c.12700) is well conserved across species and splice prediction tools suggest th at the variant may impact splicing; though this data is not predictive enough to determine pathogenicity. In summary, although additional studies are required t o fully establish its clinical significance, this variant is likely pathogenic.