Submissions for variant NM_206933.4(USH2A):c.11440G>T (p.Gly3814Ter)

dbSNP: rs727505337

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156887	SCV000206608	pathogenic	Rare genetic deafness	2014-11-12	criteria provided, single submitter	clinical testing	The p.Gly3814X variant in USH2A has not been previously reported in individuals with hearing loss and was absent from large population studies. This nonsense va riant leads to a premature termination codon at position 3814, which is predicte d to lead to a truncated or absent protein. In summary, this variant meets our c riteria to be classified as pathogenic for Usher syndrome in an autosomal recess ive manner (www.partners.org/personalizedmedicine/lmm).
Invitae	RCV002515040	SCV003345833	pathogenic	not provided	2022-04-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly3814*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 30718709). ClinVar contains an entry for this variant (Variation ID: 180084). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV003453204	SCV004182101	pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787718	SCV000926713	likely pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research