Table 3 Causative mutations and putative pathogenic variants identified in this study

From: High-throughput sequencing for the molecular diagnosis of Usher syndrome reveals 42 novel mutations and consolidates CEP250 as Usher-like disease causative

Patient	Type	Phase	Gene	Variant type	Nucleotide	Protein	Reference or Class
Patients with two pathogenic mutations
RP580M	USH II	*Het*	*ADGRV1*	Frameshift	c.5944dupT	*p.Ser1982Phefs2**	Novel UV4
		Het	ADGRV1	CNV	Dup. exons 79–83	—	Besnard et al.³⁸
RP689	USH I	Hom	MYO7A	Missense	c.1190C > A	p.Ala397Asp	Adato et al.⁶⁷
RP905	USH II	Hom	USH2A	Frameshift	c.12093delC	p.Tyr4031*	Garcia-Garcia et al.⁶¹
RP956	USH II	Hom	ADGRV1	Missense	c.17933A > G^s	p.His5978Arg	Besnard et al.³⁸
RP957	USH I	Hom	CDH23	Missense	c. 6049G > A	p.Gly2017Ser	Roux et al.⁶⁸
RP971	USH II	Het	USH2A	Nonsense	c.12729G > A	p.Trp4243*	Neveling et al.⁶⁹
		Het	USH2A	Missense	c.1531G > A	p.Glu511Lys	Baux et al.⁷⁰
RP1350	USH II	*Het*	*ADGRV1*	Nonsense	c.16886G > A	p.Trp5629*	Novel UV4
		*Het*	*ADGRV1*	Missense	c.4102A > T	p.Asn1368Tyr	Novel UV4
RP1353	USH II	*Hom*	*ADGRV1*	Splice-site	c.5314 − 5T > A	p.Asn1772*	Novel UV4
RP1399	USH II	*Hom*	*USH2A*	Nonsense	c.11404G > T	p.Glu3802*	Novel UV4
RP1420	USH I	Hom	CDH23	Nonsense	c.7221C > A	p.Tyr2407*	Besnard et al.⁵⁰
RP1495^t	USH II	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
		*Het*	*USH2A*	CNV	Del. exons 22–49	—	Novel UV4
RP1506B	USH II	*Het*	*USH2A*	Nonsense	c.10008C > A	p.Cys3336*	Novel UV4
		*Het*	*USH2A*	Nonsense	c.5416A > T	p.Lys1806*	Novel UV4
RP1564	USH II	*Hom*	*ADGRV1*	Missense	c.14159C > T ^s	p.Pro4720Leu	Novel UV4
RP1565	USH II	*Hom*	*USH2A*	Nonsense	c.11404G > T	p.Glu3802*	Novel UV4
RP1567	USH II	Het	MYO7A	Missense	c.5516T > C	p.Leu1839Pro	Aparisi et al.⁸
		*Het*	*MYO7A*	Start loss	c.3G > A	p.Met1?	Novel UV4
RP1580	USH I	Hom	MYO7A	Nonsense	c.6070C > T	p.Arg2024*	Jacobson et al.⁷¹
RP1686	USH II	*Hom*	*ADGRV1*	Nonsense	c.18054G > A	p.Trp6018*	Novel UV4
RP1694	USH I	*Hom*	*USH1G*	Missense	c.1196T > C	p.Leu399Pro	Novel UV3
RP1746^t	USH II	Het	USH2A	Missense	c.9799T > C	p.Cys3267Arg	Aller et al.⁵⁴
		Het	USH2A	Splice-site	c.12295 − 1G > A	*p.Thr4099Vfs2**	Novel UV4
RP1748	USH I	Hom	USH2A	Nonsense	c.2950C > T	p.Gln984*	Novel UV4
RP1757^t	Atypical	Het	MYO7A	IF deletion	c.655_660del^s	p.Ile219_His220del	Jaijo et al.⁶²
		*Het*	*MYO7A*	Missense	c.4489G > C^s	p.Gly1497Arg	Bonnet et al.⁵¹
RP1768^t	USH I	Het	MYO7A	Frameshift	c.1623dupC	p.Lys542Glnfs*5	Bharadwaj et al.⁶³
		Het	MYO7A	Nonsense	c.6232A > T	p.Lys2078*	Novel UV4
RP1806	USH I	Hom	USH1G	Nonsense	c.805C > T^s	p.Arg269*	Aparisi et al.⁸
RP1809	USH II	Het	USH2A	Pseudo-exon	c.7595 − 2144A > G^s	p.Lys2532Thrfs*56	Vaché et al.¹⁷
		Het	USH2A	Missense	c.12695C > T^s	p.Pro4232Leu	Bonnet et al.⁵¹
RP1811	USH II	*Hom*	*USH2A*	Nonsense	c.7932G > A	p.Trp2644*	Novel UV4
RP1857	USH I	*Het*	*CDH23*	Missense	c.3115G > A	p.Val1039Met	Novel UV3
		*Het*	*CDH23*	Missense	c.3007T > C	p.Ser1003Pro	Novel UV4
RP1869	USH II	*Hom*	*USH2A*	Missense	c.4385C > T	p.Thr1462Ile	Novel UV4
RP1872	USH II	*Hom*	*USH2A*	Splice-site	c.5776 + 1G > A ^s	p.Gly1858_Thr1925del	Novel UV4
RP1888^t	USH II	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
		Het	USH2A	CNV	Dup. exons 28–30	—	Novel UV4
RP1900	USH	Het	MYO7A	Frameshift	c.1934_1935insCCAT	*p.Met645Ilefs67**	Novel UV4
		Het	MYO7A	Splice-site	c.1691 − 1G > A	*p.Phe565Argfs11**	Novel UV4
RP1906^t	USH II	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
		*Het*	*USH2A*	Nonsense	c.9119G > A	p.Trp3040*	Novel UV4
RP1944	USH I	Hom	MYO7A	Missense	c.3503G > A	p.Arg1168Gln	Aparisi et al.⁸
RP1967	USH I	Het	MYO7A	Nonsense	c.5392C > T^s	p.Gln1798*	Bharadwaj et al.⁶³
		Het	MYO7A	Missense	c.5516T > C^s	p.Leu1839Pro	Aparisi et al.⁸
RP1969	USH I	*Hom*	*MYO7A*	Frameshift	c.5561dupT	*p.Gln1855Alafs56**	Novel UV4
RP1973	USH II	*Het*	*CEP250*	Nonsense	c.4006C > T ^s	p.Arg1336*	Novel UV4
		*Het*	*CEP250*	Nonsense	c.3337A > T ^s	p.Lys1113*	Novel UV4
RP1979	USH II	Het	USH2A	Missense	c.10712C > T	p.Thr3571Met	Aller et al.⁵⁴
		Het	USH2A	Nonsense	c.9424G > T	p.Gly3142*	Baux et al.⁷²
RP2005	USH II	*Het*	*USH2A*	Frameshift	c.4961delG	*p.Ser1654Ilefs11**	Novel UV4
		Het	USH2A	Nonsense	c.13822C > T	p.Arg4608*	Dreyer et al.⁷³
RP2007	USH I	Hom	PCDH15	Nonsense	c.1737C > G^s	p.Tyr579*	Jaijo et al.⁵⁸
RP2010	USH II	Hom	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
RP2011	USH II	Het	CDH23	Splice-site	c.6050 − 9G > A	—	von Brederlow et al.⁷⁴
		*Hom*	*ADGRV1*	CNV	Del. exons 28–33	—	Novel UV4
RP2019^t	USH	*Het*	*CDH23*	Frameshift	c.8462dupT	*p.Asp2822Argfs5**	Novel UV4
		Het	CDH23	Missense	c.4488G > C	p.Gln1496His	Bolz et al.⁶⁵
RP2022	USH II	Het	USH2A	Frameshift	c.2135delC	p.Ser712*	Bernal et al.⁷⁵
		*Het*	*USH2A*	Nonsense	c.6967C > T	p.Arg2323*	Novel UV4
RP2023	USH II	*Het*	*USH2A*	Nonsense	c.6157C > T	p.Gln2053*	Novel UV4
		Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
RP2028	USH	Het	USH2A	Nonsense	c.11864G > A	p. Trp3955*	Van Wijk et al.⁷⁶
		*Het*	*USH2A*	Frameshift	c.13778_13779insTT	p.Val4596*	Novel UV4
RP2032	USH	Het	USH2A	Missense	c.2276G > T	p.Cys759Phe	Dreyer et al.⁶⁰
		Het	USH2A	Missense	c.9799T > C	p.Cys3267Arg	Aller et al.⁵⁴
RP2035	USH	Hom	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
RP2037	USH	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
		Het	USH2A	Splice-site	c.949C > A	—	Pennings et al.⁷⁷
RP2050	USH II	Het	USH2A	Pseudo-exon	c.7595 − 2144A > G	p.Lys2532Thrfs*56	Vaché et al.¹⁷
		Het	USH2A	Missense	c.8254G > A	p.Gly2752Arg	Nakanishi et al.⁷⁸
RP2058	USH	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹
		Het	USH2A	Missense	c.802G > A	p.Gly268Arg	Baux et al.⁷⁰
RP2069	USH	*Het*	*MYO7A*	IF deletion	c.5887_5889delTTT	p.Phe1963del	Novel UV4
		Het	MYO7A	Missense	c.5648G > A	p.Arg1883Gln	Ouyang et al.⁷⁹
RP2068	USH	*Het*	*USH2A*	Frameshift	c.13102dupA	*p.Ser4368Lysfs21**	Novel UV4
		*Het*	*USH2A*	Frameshift	c.13926dupA	*p.Gln4643Thrfs40**	Novel UV4
RP1936	USH	*Het*	*ADGRV1*	Frameshift	c.1892delC	*p.Pro631Leufs62**	Novel UV4
		*Het*	*ADGRV1*	CNV	Del. Exon 85	—	Novel UV4
Patients with only one pathogenic mutation
RP681	USH	*Het*	*CDH23*	Frameshift	c.7279delA	*p.Thr2427Leufs47**	Novel UV4
RP1222	USH II	*Het*	*USH1C*	Missense	c.1234G > A	p.Asp412Asn	Novel UV3
RP1488	USH II	Het	ADGRV1	Missense	c.3151G > T	p.Asp1051Tyr	Neveling et al.⁶⁹
RP1571	USH	*Het*	*CIB2*	Missense	c.311G > A	p.Arg104Gln	Novel UV3
RP2020	USH I	Het	MYO7A	Missense	c.3508G > A	p.Glu1170Lys	Cuevas et al.⁸⁰
RP2034	USH	Het	USH2A	Frameshift	c.2299delG	p.Glu767Serfs*21	Liu et al.⁵⁹

Het, Heterozygosis; Hom, Homozygosis; PE, Pseudoexon 40; IF, In-Frame; Dup., Duplication; Del., Deletion.
^sCases where segregation analysis was performed; ^tPatients previously included in the test group.
Novel variants displayed in bold.
The novel variants found were categorized based on the guidelines of the clinical and molecular genetics society (www.emqn.org/emqn/Best+Practice) and the Unknown Variants classification system (https://grenada.lumc.nl/LOVD2/Usher_montpellier/) as pathogenic, probably pathogenic (UV4), possibly pathogenic (UV3), possibly non-pathogenic (UV2) and neutral (UV1) according to bioinformatic predictions and segregation analysis.

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Table 3 Causative mutations and putative pathogenic variants identified in this study

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