Clinical exome sequencing facilitates the understanding of genetic heterogeneity in Leber congenital amaurosis patients with variable phenotype in southern India

Table 2 Putative variants of nine South Indian patients identified by clinical exome sequencing

Patient ID	Gene	Chromosomal locus	Exon	Variant Class	Variants		Zygosity	MOI	Minor allele frequency		Functional Prediction Tools				ACMG Evidence	ACMG Classification	SNP id	Reference
Patient ID	Gene	Chromosomal locus	Exon	Variant Class	cDNA_Change	Amino acid_Change	Zygosity	MOI	ExAC	1000G	SIFT	PP2	Mutation Taster	FATHMM	ACMG Evidence	ACMG Classification	SNP id	Reference
AS01	RPE65	1p31.2	5	Frameshift-ins	c.361dup	p.Ser121PhefsTer10	Hom	AR	NA	NA	NA	NA	D	NA	PVS1, PM2, PP3, PP5	Pathogenic	rs121918844	13,14,15
AS02	LCA5	6q14.1	7	Frameshift-del	c.1062_1068del	p.Tyr354Ter	Hom	AR	NA	NA	NA	NA	D	NA	PVS1, PM2, PP3, PP5	Pathogenic	NA	17,18
AS03	LCA5	6q14.1	9	Frameshift-del	c.1823del^a	p.Leu608TyrfsTer30	Hom	AR	NA	NA	NA	NA	D	NA	PVS1, PM2, PP3	Pathogenic	NA	this study
AS04	CRX	19q13.33	4	Frameshift-del	c.848del^a	p.Met283ArgfsTer88	Het	AD	NA	NA	NA	NA	D	NA	PVS1, PM2, PP4	Pathogenic	NA	this study
AS05	PRPH2	6p21.1	2	Missense	c.629C > T	p.Pro210Leu	Hom	AR	NA	NA	D (0.03)	PoD (0.847)	D	D	PM1,PM2, PP3, PP5	Likely Pathogenic	rs61755798	24
AS06	CEP290	12q21.32	23	Missense	c.2483G > T^a	p.Ser828Ile	Hom	AR	NA	NA	D (0)	PoD (0.731)	D	T	PM2, PP3	Uncertain significance	NA	this study
AS07	ALMS1	2p13.1	16	Frameshift-del	c.11310_11313del	p.Glu3771TrpfsTer18	Hom	AR	1.67E-05	NA	NA	NA	D	NA	PVS1, PM2, PP3, PP5	Pathogenic	rs747272625	this study
AS08	IFT80	3q25.33	18	Missense	c.1936G > T	p.Val646Phe	Hom	AR	5.07E-05	NA	D (0)	PrD (0.927)	D	D	PM2, PP3	Uncertain significance	rs752617502	this study
AS09	RP1	8q12.1	4	Frameshift-del	c.3751_3752del	p.Val1251PhefsTer9	Hom	AR	8.24E-06	NA	NA	NA	D	NA	PVS1, PM2, PP3	Pathogenic	rs745640645	this study

Hom = homozygous; Het = heterozygous; MOI = mode of inheritance; AR = autosomal recessive; AD = autosomal dominant. NA = not available, SIFT (score: 1 to 0); D = deleterious (≤ 0.05); T = tolerated (> 0.05), PP2 (score: 0 to 1); PrD = probably damaging (≥ 0.909); PoD = possibly damaging (≥ 0.447); B = benign (≤ 0.446), mutation taster; D = diseases causing, FATHMM (0 to 1); D = deleterious (> 0.45); T = tolerated (< 0.45), ^aNovel mutations

ISSN: 2326-0254