Table 3.
Summary of EYS variants identified.
| Patient | Variant | Protein | Genotype | Exon | Location on Chr 6 | gnomAD MAF | Polyphen2 | SIFT | Mutation taster | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| A | c.8196_8200delCTTTC | p.(Phe2733fs33*) | Hom | 43 | 64,436,508–512 | 0.00006 (Hom 0) | N/A | N/A | D | [19] |
| B | c.7672_7673delTA | p.(Tyr2558fs12*) | Het | 39 | 64,498,048–049 | 0 | N/A | N/A | D | Novel |
| c.8842T>C | p.(Cys2948Arg) | Het | 44 | 64,431,148 | 0.00004 | D | D | D | [32] | |
| C | c.8897G>A | p.(Gly2966Glu) | Het | 44 | 64,431,093 | 0.00002 | D | D | D | [33] |
| c.9452_9454delAAG | p.(Glu3151del) | Het | 44 | 64,430,536–538 | 0.000008 | N/A | N/A | D | Novel | |
| D | c.1308C>A | p.(Cys436*) | Hom | 9 | 66,063,502 | 0.000004 (Hom 0) | N/A | N/A | D | [9] |
| E | c.5834delA | p.(Lys1945fs42*) | Hom | 27 | 65,149,056 | 0.00005 (Hom 0) | N/A | N/A | D | [34] |
| F | c.7868G>A | p.(Gly2623Glu) | Het | 40 | 64,487,929 | 0.0008 | D | D | T | [25] |
| c.8196_8200delCTTTC | p.(Phe2733fs33*) | Het | 43 | 64,436,508–512 | 0.00006 | N/A | N/A | D | [19] | |
| G | c.6389G>C | p.(Cys2130Ser) | Het | 31 | 64,940,520 | 0.000007 | D | D | T | Novel |
| c.9159_9165delGAGCTAT | p.(Met3053fs16*) | Het | 44 | 64,430,825–831 | 0 | N/A | N/A | D | Novel | |
| H | c.8054G>A | p.(Gly2685Glu) | Het | 41 | 64,472,371 | 0.00002 | D | D | D | [11] |
| c.9446_9450delAATTA | p.(Lys3149fs7*) | Het | 44 | 64,430,540–544 | 0 | N/A | N/A | D | [35] | |
| I | c.76C>T | p.(Arg26Trp) | Het | 4 | 66,205,228 | 0.00002 | N | T | T | Novel |
| c.4723T>G | p.(Leu1575Val) | Het | 26 | 65,301,037 | 0.00002 | N | N/A | D | Novel | |
| J | c.2137 + 1G>A | Splicing | Het | IVS13 | 65,767,506 | 0.0007 | N/A | N/A | N/A | [21] |
| c.6050G>T | p.(Gly2017Val) | Het | 29 | 65,098,611 | 0.00003 | D | D | D | [33] | |
| K | c.8868C>A | p.(Tyr2956*) | Het | 44 | 64,431,122 | 0.00003 | N/A | D | D | [36] |
| dupExon14 | Het | 14 | 65,707,475–596 | 0 | N/A | N/A | N/A | [37] | ||
| L | c.6389G>C | p.(Cys2130Ser | Hom | 31 | 64,940,520 | 0.000007 (Hom 0) | D | D | T | Novel |
Chromosome position is based on build GRCh37/hg19; Nucleotide and protein numbering is based on EYS transcript NM_001142800. Novel variants identified in this study are shaded.
Polyphen predictions range from 0 to 1 and variants are appraised qualitatively as benign (B) (0.00–0.15), possibly damaging (P) (0.16–0.85), or probably damaging (D) (0.86–1.00).
SIFT results are reported to be tolerant (T) if tolerance index >0.05 or intolerant (deleterious (D)) if tolerance ≤0.05.
Mutation Taster predicts a sequence change as one of four types: disease causing (D, probably deleterious), disease causing automatic (A, known to be deleterious), polymorphism (T, probably harmless) or polymorphism automatic (B, known to be harmless).
gnomAD, Polyphen, SIFT, and Mutation Taster were accessed in January 2020.
Het heterozygote, Hom homozygote, MAF minor allele frequency, gnomAD Genome Aggregation Database, N/A not applicable.