Submissions for variant NM_206933.4(USH2A):c.6929C>T (p.Thr2310Met)

gnomAD frequency: 0.00007  dbSNP: rs151057466

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001239617	SCV001412501	pathogenic	not provided	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 2310 of the USH2A protein (p.Thr2310Met). This variant is present in population databases (rs151057466, gnomAD 0.03%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 30733538, 31054281, 32188678, 32675063, 33576794; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 965224). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. This variant disrupts the p.Thr2310 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 28944237), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376450	SCV001573591	uncertain significance	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.6929C>T 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.
DBGen Ocular Genomics	RCV001376450	SCV001816010	likely pathogenic	Retinitis pigmentosa 39	2021-06-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001376450	SCV004208237	likely pathogenic	Retinitis pigmentosa 39	2024-03-29	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001239617	SCV001920417	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001239617	SCV001955252	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001834098	SCV002090870	uncertain significance	Usher syndrome type 2A	2020-09-28	no assertion criteria provided	clinical testing