Submissions for variant NM_206933.4(USH2A):c.9815C>T (p.Pro3272Leu)

gnomAD frequency: 0.00001  dbSNP: rs764182950

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668871	SCV000793544	likely pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2017-08-18	criteria provided, single submitter	clinical testing
Mendelics	RCV000986527	SCV001135542	pathogenic	Usher syndrome type 2A	2019-05-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001073802	SCV001239364	likely pathogenic	Retinal dystrophy	2018-04-11	criteria provided, single submitter	clinical testing
Invitae	RCV001209780	SCV001381230	pathogenic	not provided	2023-09-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 553424). This missense change has been observed in individual(s) with USH2A-related conditions (PMID: 18281613, 25575603, 26338283, 26667666, 27157150, 29142287). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs764182950, gnomAD 0.02%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3272 of the USH2A protein (p.Pro3272Leu).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001724125	SCV001950419	likely pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Pro3272Leu variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3-S. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Revvity Omics, Revvity	RCV001209780	SCV003826119	pathogenic	not provided	2021-11-24	criteria provided, single submitter	clinical testing
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation	RCV003389477	SCV003927137	likely pathogenic	Usher syndrome	2022-12-31	criteria provided, single submitter	research
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV001724125	SCV004030348	likely pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Genome-Nilou Lab	RCV000678659	SCV004182654	likely pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000986527	SCV004182655	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000678659	SCV004208192	pathogenic	Retinitis pigmentosa 39	2024-02-06	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000678659	SCV000804751	uncertain significance	Retinitis pigmentosa 39	2016-09-01	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000986527	SCV002088384	pathogenic	Usher syndrome type 2A	2021-04-05	no assertion criteria provided	clinical testing