Submissions for variant NM_206933.4(USH2A):c.1226G>A (p.Trp409Ter)

dbSNP: rs2037682180

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001237068	SCV001409818	pathogenic	not provided	2024-05-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp409*) 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 Usher syndrome type 2 and autosomal recessive retinitis pigmentosa (PMID: 26927203, 27318125). ClinVar contains an entry for this variant (Variation ID: 963094). For these reasons, this variant has been classified as Pathogenic.
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation	RCV003389490	SCV003927069	pathogenic	Usher syndrome	2022-12-31	criteria provided, single submitter	research
Neuberg Centre For Genomic Medicine, NCGM	RCV003388606	SCV004100403	pathogenic	Usher syndrome type 2A		criteria provided, single submitter	clinical testing	The stop gained p.W409* in USH2A (NM_206933.4) variant has been observed in individuals affected with Usher syndrome type 2 and autosomal recessive retinitis pigmentosa ( Bas P Hartel et al 2016; Laurence H M Pierrache et al 2016 ). The variant has been submitted to ClinVar as Pathogenic. Loss-of-function variants in USH2A are known to be pathogenic. The p.W409* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Pathogenic. A different heterozygous variant in the USH2A gene has been detected in the spouse.
Genome-Nilou Lab	RCV003388606	SCV004182900	pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003462803	SCV004208161	likely pathogenic	Retinitis pigmentosa 39	2023-12-10	criteria provided, single submitter	clinical testing
Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare	RCV003388606	SCV005873722	likely pathogenic	Usher syndrome type 2A	2021-03-10	criteria provided, single submitter	clinical testing