VCV000197932.94 - ClinVar

NM_206933.4(USH2A):c.10073G>A (p.Cys3358Tyr)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (17); Likely pathogenic (11)

28 out of 35 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_206933.4(USH2A):c.10073G>A (p.Cys3358Tyr)

Variation ID: 197932 Accession: VCV000197932.94

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q41 1: 215790168 (GRCh38) [ NCBI UCSC ] 1: 215963510 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 28, 2015	Jun 20, 2026	Mar 29, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_206933.4:c.10073G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_996816.3:p.Cys3358Tyr	missense
NM_206933.3:c.10073G>A
NC_000001.11:g.215790168C>T
NC_000001.10:g.215963510C>T
NG_009497.2:g.638281G>A
	O75445:p.Cys3358Tyr

... more HGVS ... less HGVS

Protein change

C3358Y

Other names

NM_206933.2(USH2A):c.10073G>A(p.Cys3358Tyr)
NP_996816.3:p.(Cys3358Tyr)

Canonical SPDI

NC_000001.11:215790167:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.00029

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054

The Genome Aggregation Database (gnomAD) 0.00056

The Genome Aggregation Database (gnomAD), exomes 0.00035

Trans-Omics for Precision Medicine (TOPMed) 0.00050

The Genome Aggregation Database (gnomAD) 0.00052

Links

ClinGen: CA275315 UniProtKB: O75445#VAR_068356 dbSNP: rs148660051 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
USH2A		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	8076	9788

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Retinitis pigmentosa 39	Pathogenic/Likely pathogenic (8)	criteria provided, multiple submitters, no conflicts	May 8, 2025	RCV000179099.15
Usher syndrome type 2A	Pathogenic/Likely pathogenic (9)	criteria provided, multiple submitters, no conflicts	Aug 5, 2025	RCV000190637.20
not provided	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV000482080.60
Retinitis pigmentosa	Pathogenic/Likely pathogenic (5)	criteria provided, multiple submitters, no conflicts	Jul 24, 2023	RCV000505000.13
Retinitis pigmentosa 39 Usher syndrome type 2A	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 4, 2024	RCV000515419.8
Retinal dystrophy	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 1, 2023	RCV001073681.4
Usher syndrome	Pathogenic (1)	criteria provided, single submitter	May 11, 2022	RCV001174974.3
USH2A-related disorder	Pathogenic (1)	no assertion criteria provided	Mar 13, 2024	RCV004537478.2
Monogenic hearing loss	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2026	RCV006697872.1
Retinal disorder	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2026	RCV006697871.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Jan 27, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A	Knight Diagnostic Laboratories, Oregon Health and Sciences University Study: CSER-NextGen Accession: SCV000538073.1 First in ClinVar: Apr 03, 2017 Last updated: Apr 03, 2017	Comment: show The c.10073G>A (p.Cys3358Tyr) missense variant in the USH2A gene has been previously reported in several individuals affected with Usher Syndrome or Retinitis Pigmentosa. This allele was observed in 13 cases out of 914 affected alleles (Lenassi et al., 2015) and is significantly higher than the allele frequency in the ExAC database (13/121292). This variant is often seen in trans with other pathogenic variants (Garcia-Garcia et al., 2011; Le Quesne Stabej et al., 2012; Neveling et al., 2012; Lenassi et al., 2015). This c.10073G>A allele has been reported at low frequency, or is absent in other population databases (Exome Sequencing Project [ESP] = 0.058%, 1000 Genomes = NA). Multiple in silico algorithms predict this variant to have a deleterious effect GERP = 5.76; CADD = 22.4; PolyPhen = 1; SIFT = 0). Reputable diagnostic laboratories have reported this variant as either Likely Pathogenic or Pathogenic for either, Retinitis Pigmentosa or Usher Syndrome, Type 2A. Therefore, this collective evidence supports the classification of the c.10073G>A (p.Cys3358Tyr) as a recessive Likely Pathogenic variant for Usher syndrome, type IIA. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely pathogenic (Sep 30, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A	Baylor Genetics Accession: SCV001520105.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Publications: PubMed (4) PubMed: 20507924‚ 22004887‚ 25097241‚ 25472526 Comment: show This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing by following sources [PMID: 25097241, 20507924, 25472526, 22004887, ClinVar ID: 197932] (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes

Pathogenic (Mar 29, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	Baylor Genetics Accession: SCV004207688.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Apr 05, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000231295.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Publications: PubMed (5) PubMed: 20507924‚ 22004887‚ 22135276‚ 22334370‚ 25649381 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 5 Zygosity: 5 Single Heterozygotes Sex: mixed

Pathogenic (Jan 25, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A Retinitis pigmentosa 39 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Department of Pathology and Laboratory Medicine, Sinai Health System Accession: SCV006059172.1 First in ClinVar: Apr 28, 2025 Last updated: Apr 28, 2025	Observation: 1 Collection method: research Allele origin: germline Affected status: unknown Observation 1 Collection method: research Allele origin: germline Affected status: unknown

Pathogenic (Mar 29, 2026) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2024 v1.2)	Retinal disorders	Genetics Laboratory, Great Ormond Street Hospital NHS Foundation Trust, North Thames Genomic Laboratory Hub Accession: SCV007596938.1 First in ClinVar: May 30, 2026 Last updated: May 30, 2026	Comment: show PS4_moderate, PM3_very-strong (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Mar 29, 2026) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2024 v1.2)	Monogenic hearing loss	Genetics Laboratory, Great Ormond Street Hospital NHS Foundation Trust, North Thames Genomic Laboratory Hub Accession: SCV007596939.1 First in ClinVar: May 30, 2026 Last updated: May 30, 2026	Comment: show PS4_moderate, PM3_very-strong (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Dec 17, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Usher syndrome type 2A	Myriad Genetics, Inc. Accession: SCV001193786.1 First in ClinVar: Apr 06, 2020 Last updated: Apr 06, 2020	Publications: PubMed (7) PubMed: 20507924‚ 22004887‚ 22334370‚ 25097241‚ 25472526‚ 25649381‚ 26667666 Comment: show NM_206933.2(USH2A):c.10073G>A(C3358Y) is classified as likely pathogenic in the context of USH2A-related disorders and is primarily associated with retinitis pigmentosa. Sources cited for classification include the following: PMID 22004887, 22334370, 26667666, 25472526, 25097241, 25649381 and 20507924. Classification of NM_206933.2(USH2A):c.10073G>A(C3358Y) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Aug 15, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Retinal dystrophy	Blueprint Genetics Accession: SCV001239234.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 Comment: My Retina Tracker patient	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Apr 08, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	Ocular Genomics Institute, Massachusetts Eye and Ear Accession: SCV001573662.1 First in ClinVar: May 10, 2021 Last updated: May 10, 2021	Publications: PubMed (8) PubMed: 20507924‚ 21151602‚ 22004887‚ 22135276‚ 25097241‚ 25472526‚ 25649381‚ 26667666 Comment: show The USH2A c.10073G>A 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: PS1, PM2, PM3, PP3. Based on this evidence we have classified this variant as Likely Pathogenic. (less) Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Pathogenic (Mar 29, 2021) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	Retinitis pigmentosa (Autosomal recessive inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000245680.5 First in ClinVar: Sep 14, 2015 Last updated: May 29, 2021	Publications: PubMed (11) PubMed: 20507924‚ 21151602‚ 22004887‚ 22135276‚ 22334370‚ 25097241‚ 25472526‚ 25649381‚ 25999674‚ 28559085‚ 29953849 Comment: show The p.Cys3358Tyr variant in USH2A has been reported in over 15 individuals with retinitis pigmentosa, with at least 9 of these individuals being compound heterozygous for a pathogenic variant on the remaining copy of USH2A (Calzetti 2018 PMID:29953849, Garcia-Garcia 2011 PMID:22004887, LeQuesne Stabej 2012 PMID:22135276, Lenassi 2015 PMID:25649381, McGee 2010 PMID:20507924, Neveling 2012 PMID:22334370, Stone 2018 PMID:28559085, van Huet 2015 PMID:25999674, Wang 2014 PMID:25097241, Zhao 2015 PMID:25472526, Avila-Fernandez 2010 PMID:21151602). Two of these individuals were reported to have features of atypical type 2 Usher syndrome, with a later onset hearing loss (Garcia-Garcia 2011 PMID:22004887, Lenassi 2015 PMID:25649381), and one was reported to have hearing loss though age of onset was not noted (Calzetti 2018 PMID:29953849). The variant has been identified in 98/128872 European chromosomes by gnomAD (http://gnomad.broadinstitute.org); however its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analysis suggest an impact to the protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive retinitis pigmentosa and/or atypical type 2 Usher syndrome, based on the previously reported individuals. ACMG/AMP criteria applied: PM3_VeryStrong, PM2_Supporting, PP3. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 4

Likely pathogenic (Apr 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa (Autosomal recessive inheritance)	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV001950390.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Publications: PubMed (9) PubMed: 20507924‚ 21151602‚ 22004887‚ 22135276‚ 25097241‚ 25472526‚ 25649381‚ 26667666‚ 34906470 Comment: show The p.Cys3358Tyr 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: PS1, PM2, PM3, PP3. 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. (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Pathogenic (May 11, 2022) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Usher syndrome	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001338457.2 First in ClinVar: Jun 18, 2020 Last updated: Jul 17, 2022	Publications: PubMed (8) PubMed: 20507924‚ 22004887‚ 22135276‚ 22334370‚ 25097241‚ 25649381‚ 29953849‚ 32531858 Comment: show Variant summary: USH2A c.10073G>A (p.Cys3358Tyr) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251094 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (0.00035 vs 0.011), allowing no conclusion about variant significance. c.10073G>A has been reported in the literature in multiple individuals affected with Usher Syndrome/Retinitis Pigmentosa/Inherited Retinal Diseases (IRD) (example, Garcia-Garcia_2011, LeQuesneStabej_2012, Lenassi_2015, Neveling_2012, Wang_2014, Calzetti_2018, McGee_2010, Weisschuh_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Nov 04, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	Genome-Nilou Lab Accession: SCV004182598.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely pathogenic (Nov 04, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A	Genome-Nilou Lab Accession: SCV004182599.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely pathogenic (Jan 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinal dystrophy	Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg Accession: SCV005068677.1 First in ClinVar: Dec 28, 2024 Last updated: Dec 28, 2024	Publications: PubMed (24) PubMed: 20507924‚ 22004887‚ 25097241‚ 25472526‚ 28559085‚ 29953849‚ 31456290‚ 31589614‚ 31964843‚ 31980526‚ 32037395‚ 32176120‚ 32326409‚ 32531858‚ 32581362‚ 33258288‚ 33576794‚ 33737949‚ 33749171‚ 34758253‚ 35266249‚ 36011334‚ 36672815‚ 36819107 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Feb 02, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A (Autosomal recessive inheritance)	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Accession: SCV002557348.2 First in ClinVar: Aug 08, 2022 Last updated: Jul 23, 2024	Publications: PubMed (2) PubMed: 22004887‚ 25649381 Comment: show Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Usher syndrome, type 2A (MIM#276901) and retinitis pigmentosa (MIM# 6138093). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 111 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals with both Usher syndrome, type 2A (MIM#276901) and retinitis pigmentosa (MIM# 6138093), and classified as both like pathogenic and pathogenic by diagnostic laboratories in Clinvar (PMID: 22004887, 25649381). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Oct 28, 2024) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000565648.8 First in ClinVar: Apr 27, 2017 Last updated: Nov 10, 2024	Comment: show In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28559085, 32531858, 34758253, 22334370, 25472526, 22004887, 20507924, 25649381, 22135276, 21151602, 25999674, 25097241, 26667666, 29953849, 31456290, 31980526, 32176120, 32581362, 31589614, 33576794, 33258288, 33737949, 32037395, 32326409, 36011334, 35266249, 38219857, 37217489, 36672815, 34906470, 31964843, 36819107, 33749171, 36646238, 38351866, 36909829) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Jun 04, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A Retinitis pigmentosa 39 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Fulgent Genetics, Fulgent Genetics Accession: SCV000611246.3 First in ClinVar: Nov 11, 2017 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Mar 05, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Revvity Omics, Revvity Accession: SCV002021605.4 First in ClinVar: Nov 29, 2021 Last updated: Sep 06, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Feb 12, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 2A	Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare Accession: SCV007100162.1 First in ClinVar: Nov 15, 2025 Last updated: Nov 15, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000952339.8 First in ClinVar: Aug 14, 2019 Last updated: Mar 07, 2026	Publications: PubMed (4) PubMed: 22004887‚ 22135276‚ 25472526‚ 28559085 Comment: show This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 3358 of the USH2A protein (p.Cys3358Tyr). This variant is present in population databases (rs148660051, gnomAD 0.07%). This missense change has been observed in individual(s) with Usher syndrome or retinal disease (PMID: 22004887, 22135276, 25472526, 28559085). 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: 197932). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 01, 2018) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV001246252.38 First in ClinVar: May 09, 2020 Last updated: Jun 20, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely pathogenic (May 08, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	3billion Accession: SCV006582767.2 First in ClinVar: Oct 25, 2025 Last updated: Jun 20, 2026	Publications: PubMed (1) PubMed: 20507924 Comment: show The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.100%). Predicted Consequence/Location: Missense variant. The majority of the known disease-causing variants of this gene are variants expected to result in premature termination of the protein. In silico tool predictions suggest damaging effect of the variant on gene or gene product [3Cnet: 0.95 (> 0.75, sensitivity 0.96 and precision 0.92)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000197932 /PMID: 20507924 /3billion dataset). A different missense change at the same codon (p.Cys3358Ser) has been reported to be associated with USH2A-related disorder (ClinVar ID: VCV002920650). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Platform type: exome sequencing

Likely pathogenic (May 31, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	SIB Swiss Institute of Bioinformatics Accession: SCV000803576.1 First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015	Publications: PubMed (2) PubMed: 22334370‚ 25649381 Comment: show This variant is interpreted as a Likely Pathogenic, for Retinitis pigmentosa 39, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM3-Strong => PM3 upgraded in strength to Strong (PMID:22334370) (PMID:25649381). (less) Observation: 1 Collection method: curation Allele origin: unknown Affected status: unknown Observation 1 Collection method: curation Allele origin: unknown Affected status: unknown

Pathogenic (Sep 27, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa 39	Genetics and Molecular Pathology, SA Pathology Accession: SCV002556913.2 First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Jul 24, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Retinitis pigmentosa	Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel Accession: SCV004030329.2 First in ClinVar: Sep 03, 2023 Last updated: Apr 13, 2025 Comment: This variant was classified as Pathogenic based on ACMG criteria: PP5, PM2, PS4.	Publications: PubMed (1) PubMed: 36909829 Comment: show Clinical significance based on ACMG v2.0 (less) Observation: 1 Collection method: research Allele origin: germline Affected status: yes more Observation 1 Collection method: research Allele origin: germline Affected status: yes Number of individuals with the variant: 1 Sex: male Geographic origin: Portugal

Pathogenic (Aug 05, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Usher syndrome type 2A	Natera, Inc. Accession: SCV007530063.1 First in ClinVar: Apr 04, 2026 Last updated: Apr 04, 2026	Publications: PubMed (1) PubMed: 29953849 Comment: show The c.10073G>A variant in USH2A is a missense variant predicted to cause substitution of cysteine to tyrosine at amino acid 3358. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 29953849). Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Jul 19, 2016) N Not contributing to aggregate classification	no assertion criteria provided	Usher syndrome type 2A	Division of Human Genetics, Children's Hospital of Philadelphia Study: CSER-PediSeq Accession: SCV000536900.1 First in ClinVar: Apr 03, 2017 Last updated: Apr 03, 2017	Publications: PubMed (4) PubMed: 20507924‚ 22004887‚ 25097241‚ 25472526 Observation: 1 Collection method: research Allele origin: paternal Affected status: yes Observation 1 Collection method: research Allele origin: paternal Affected status: yes

Likely pathogenic (Jun 23, 2019) N Not contributing to aggregate classification	no assertion criteria provided	Retinitis pigmentosa	Sharon lab, Hadassah-Hebrew University Medical Center Accession: SCV001161345.1 First in ClinVar: Feb 17, 2020 Last updated: Feb 17, 2020	Observation: 1 Collection method: research Allele origin: inherited Affected status: yes Observation 1 Collection method: research Allele origin: inherited Affected status: yes

Pathogenic (Mar 13, 2024) N Not contributing to aggregate classification	no assertion criteria provided	USH2A-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004112532.2 First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024	Comment: show The USH2A c.10073G>A variant is predicted to result in the amino acid substitution p.Cys3358Tyr. This variant has been reported along with a second pathogenic variant in many individuals with autosomal recessive nonsyndromic retinitis pigmentosa or Usher syndrome (Calzetti et al. 2018. PubMed ID: 29953849; Table S4, Colombo et al. 2021. PubMed ID: 33576794; Lynn et al. 2023. PubMed ID: 36672815; Molina-Ramírez et al. 2020. PubMed ID: 32176120; Table S4, Panneman et al. 2023. PubMed ID: 36819107), although it has been associated primarily with nonsyndromic retinal degeneration in patients without early onset hearing loss (Leanassi et al. 2015. PubMed ID: 25649381). This variant is reported in 0.076% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Dec 16, 2016) N Not contributing to aggregate classification	no assertion criteria provided	Retinitis pigmentosa 39	Counsyl Accession: SCV000678128.3 First in ClinVar: Jan 06, 2018 Last updated: Jun 29, 2025	Publications: PubMed (7) PubMed: 20507924‚ 22004887‚ 22334370‚ 25097241‚ 25472526‚ 25649381‚ 26667666 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided (ACGS Guidelines, 2016)	Retinitis pigmentosa 39	Genomics England Pilot Project, Genomics England Accession: SCV001760012.1 First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Aug 25, 2021) N Not contributing to aggregate classification	no assertion criteria provided	Usher syndrome type 2A	Clinical Genetics Laboratory, University Hospital Schleswig-Holstein Accession: SCV002011779.1 First in ClinVar: Nov 05, 2021 Last updated: Nov 05, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Jan 01, 2015) N Not contributing to aggregate classification	no assertion criteria provided	Retinitis pigmentosa	NIHR Bioresource Rare Diseases, University of Cambridge Accession: SCV000598759.2 First in ClinVar: Sep 09, 2017 Last updated: Apr 13, 2025	Publications: PubMed (2) PubMed: 20507924‚ 28041643 Observation: 6 Observation 1 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European Platform type: Whole Genome Sequencing Observation 2 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: European Platform type: Whole Genome Sequencing Observation 3 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: European Platform type: Whole Genome Sequencing Observation 4 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European Platform type: Whole Genome Sequencing Observation 5 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European Platform type: Whole Genome Sequencing Observation 6 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: European Platform Type: Whole Genome Sequencing

Comment:

The c.10073G>A (p.Cys3358Tyr) missense variant in the USH2A gene has been previously reported in several individuals affected with Usher Syndrome or Retinitis Pigmentosa. This allele was observed in 13 cases out of 914 affected alleles (Lenassi et al., 2015) and is significantly higher than the allele frequency in the ExAC database (13/121292). This variant is often seen in trans with other pathogenic variants (Garcia-Garcia et al., 2011; Le Quesne Stabej et al., 2012; Neveling et al., 2012; Lenassi et al., 2015). This c.10073G>A allele has been reported at low frequency, or is absent in other population databases (Exome Sequencing Project [ESP] = 0.058%, 1000 Genomes = NA). Multiple in silico algorithms predict this variant to have a deleterious effect GERP = 5.76; CADD = 22.4; PolyPhen = 1; SIFT = 0). Reputable diagnostic laboratories have reported this variant as either Likely Pathogenic or Pathogenic for either, Retinitis Pigmentosa or Usher Syndrome, Type 2A. Therefore, this collective evidence supports the classification of the c.10073G>A (p.Cys3358Tyr) as a recessive Likely Pathogenic variant for Usher syndrome, type IIA.

Comment:

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing by following sources [PMID: 25097241, 20507924, 25472526, 22004887, ClinVar ID: 197932]

Comment:

NM_206933.2(USH2A):c.10073G>A(C3358Y) is classified as likely pathogenic in the context of USH2A-related disorders and is primarily associated with retinitis pigmentosa. Sources cited for classification include the following: PMID 22004887, 22334370, 26667666, 25472526, 25097241, 25649381 and 20507924. Classification of NM_206933.2(USH2A):c.10073G>A(C3358Y) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

Comment:

The USH2A c.10073G>A 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: PS1, PM2, PM3, PP3. Based on this evidence we have classified this variant as Likely Pathogenic.

Comment:

The p.Cys3358Tyr variant in USH2A has been reported in over 15 individuals with retinitis pigmentosa, with at least 9 of these individuals being compound heterozygous for a pathogenic variant on the remaining copy of USH2A (Calzetti 2018 PMID:29953849, Garcia-Garcia 2011 PMID:22004887, LeQuesne Stabej 2012 PMID:22135276, Lenassi 2015 PMID:25649381, McGee 2010 PMID:20507924, Neveling 2012 PMID:22334370, Stone 2018 PMID:28559085, van Huet 2015 PMID:25999674, Wang 2014 PMID:25097241, Zhao 2015 PMID:25472526, Avila-Fernandez 2010 PMID:21151602). Two of these individuals were reported to have features of atypical type 2 Usher syndrome, with a later onset hearing loss (Garcia-Garcia 2011 PMID:22004887, Lenassi 2015 PMID:25649381), and one was reported to have hearing loss though age of onset was not noted (Calzetti 2018 PMID:29953849). The variant has been identified in 98/128872 European chromosomes by gnomAD (http://gnomad.broadinstitute.org); however its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analysis suggest an impact to the protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive retinitis pigmentosa and/or atypical type 2 Usher syndrome, based on the previously reported individuals. ACMG/AMP criteria applied: PM3_VeryStrong, PM2_Supporting, PP3.

Comment:

The p.Cys3358Tyr 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: PS1, PM2, PM3, PP3. 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.

Comment:

Variant summary: USH2A c.10073G>A (p.Cys3358Tyr) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251094 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (0.00035 vs 0.011), allowing no conclusion about variant significance. c.10073G>A has been reported in the literature in multiple individuals affected with Usher Syndrome/Retinitis Pigmentosa/Inherited Retinal Diseases (IRD) (example, Garcia-Garcia_2011, LeQuesneStabej_2012, Lenassi_2015, Neveling_2012, Wang_2014, Calzetti_2018, McGee_2010, Weisschuh_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Usher syndrome, type 2A (MIM#276901) and retinitis pigmentosa (MIM# 6138093). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 111 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals with both Usher syndrome, type 2A (MIM#276901) and retinitis pigmentosa (MIM# 6138093), and classified as both like pathogenic and pathogenic by diagnostic laboratories in Clinvar (PMID: 22004887, 25649381). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

Comment:

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28559085, 32531858, 34758253, 22334370, 25472526, 22004887, 20507924, 25649381, 22135276, 21151602, 25999674, 25097241, 26667666, 29953849, 31456290, 31980526, 32176120, 32581362, 31589614, 33576794, 33258288, 33737949, 32037395, 32326409, 36011334, 35266249, 38219857, 37217489, 36672815, 34906470, 31964843, 36819107, 33749171, 36646238, 38351866, 36909829)

Comment:

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 3358 of the USH2A protein (p.Cys3358Tyr). This variant is present in population databases (rs148660051, gnomAD 0.07%). This missense change has been observed in individual(s) with Usher syndrome or retinal disease (PMID: 22004887, 22135276, 25472526, 28559085). 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: 197932). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

Comment:

The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.100%). Predicted Consequence/Location: Missense variant. The majority of the known disease-causing variants of this gene are variants expected to result in premature termination of the protein. In silico tool predictions suggest damaging effect of the variant on gene or gene product [3Cnet: 0.95 (> 0.75, sensitivity 0.96 and precision 0.92)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000197932 /PMID: 20507924 /3billion dataset). A different missense change at the same codon (p.Cys3358Ser) has been reported to be associated with USH2A-related disorder (ClinVar ID: VCV002920650). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

This variant is interpreted as a Likely Pathogenic, for Retinitis pigmentosa 39, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM3-Strong => PM3 upgraded in strength to Strong (PMID:22334370) (PMID:25649381).

Comment:

The c.10073G>A variant in USH2A is a missense variant predicted to cause substitution of cysteine to tyrosine at amino acid 3358. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 29953849). Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Pathogenic.

Comment:

The USH2A c.10073G>A variant is predicted to result in the amino acid substitution p.Cys3358Tyr. This variant has been reported along with a second pathogenic variant in many individuals with autosomal recessive nonsyndromic retinitis pigmentosa or Usher syndrome (Calzetti et al. 2018. PubMed ID: 29953849; Table S4, Colombo et al. 2021. PubMed ID: 33576794; Lynn et al. 2023. PubMed ID: 36672815; Molina-Ramírez et al. 2020. PubMed ID: 32176120; Table S4, Panneman et al. 2023. PubMed ID: 36819107), although it has been associated primarily with nonsyndromic retinal degeneration in patients without early onset hearing loss (Leanassi et al. 2015. PubMed ID: 25649381). This variant is reported in 0.076% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.	Peter VG	PNAS nexus	2023	PMID: 36909829
Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis.	Panneman DM	Frontiers in cell and developmental biology	2023	PMID: 36819107
Genetic Diagnosis for 64 Patients with Inherited Retinal Disease.	Lynn J	Genes	2022	PMID: 36672815
Phenotypic and Genetic Characteristics in a Cohort of Patients with Usher Genes.	Feenstra HM	Genes	2022	PMID: 36011334
Tissue-specific genotype-phenotype correlations among USH2A-related disorders in the RUSH2A study.	Hufnagel RB	Human mutation	2022	PMID: 35266249
The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK).	Zampaglione E	Genetics in medicine : official journal of the American College of Medical Genetics	2022	PMID: 34906470
100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.	100,000 Genomes Project Pilot Investigators	The New England journal of medicine	2021	PMID: 34758253
Panel-based genetic testing for inherited retinal disease screening 176 genes.	Sheck LHN	Molecular genetics & genomic medicine	2021	PMID: 33749171
Identification of Deep-Intronic Splice Mutations in a Large Cohort of Patients With Inherited Retinal Diseases.	Qian X	Frontiers in genetics	2021	PMID: 33737949
Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome.	Colombo L	Investigative ophthalmology & visual science	2021	PMID: 33576794
Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases.	Quaio CRDC	American journal of medical genetics. Part C, Seminars in medical genetics	2020	PMID: 33258288
Whole-genome sequencing of patients with rare diseases in a national health system.	Turro E	Nature	2020	PMID: 32581362
Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9-year period.	Weisschuh N	Human mutation	2020	PMID: 32531858
Comparative Analysis of Functional and Structural Decline in Retinitis Pigmentosas.	Cabral T	International journal of molecular sciences	2020	PMID: 32326409
Establishing Genotype-phenotype Correlation in USH2A-related Disorders to Personalize Audiological Surveillance and Rehabilitation.	Molina-Ramírez LP	Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology	2020	PMID: 32176120
Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations.	Zampaglione E	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 32037395
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.	Hou YC	Proceedings of the National Academy of Sciences of the United States of America	2020	PMID: 31980526
Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases.	Hanany M	Proceedings of the National Academy of Sciences of the United States of America	2020	PMID: 31964843
A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).	Sharon D	Human mutation	2020	PMID: 31456290
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.	Capalbo A	PLoS genetics	2019	PMID: 31589614
Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation.	Calzetti G	American journal of ophthalmology	2018	PMID: 29953849
Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease.	Stone EM	Ophthalmology	2017	PMID: 28559085
NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa.	Ge Z	Scientific reports	2015	PMID: 26667666
The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice.	van Huet RA	Molecular vision	2015	PMID: 25999674
A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.	Lenassi E	European journal of human genetics : EJHG	2015	PMID: 25649381
Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland.	Zhao L	Human genetics	2015	PMID: 25472526
Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa.	Wang J	Investigative ophthalmology & visual science	2014	PMID: 25097241
Next-generation genetic testing for retinitis pigmentosa.	Neveling K	Human mutation	2012	PMID: 22334370
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.	Le Quesne Stabej P	Journal of medical genetics	2012	PMID: 22135276
Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations.	Garcia-Garcia G	Orphanet journal of rare diseases	2011	PMID: 22004887
Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.	Ávila-Fernández A	Molecular vision	2010	PMID: 21151602
Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.	McGee TL	Journal of medical genetics	2010	PMID: 20507924
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A	-	-	-	-
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Text-mined citations for rs148660051 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 27, 2026