ABCMdb

ABCA4 p.Lys2160Glu

ClinVar:	c.6479A>G , p.Lys2160Arg ? , not provided
Predicted by SNAP2:	A: D (63%), C: D (66%), D: D (59%), E: D (53%), F: D (71%), G: D (59%), H: D (53%), I: D (63%), L: D (63%), M: D (63%), N: N (66%), P: D (63%), Q: N (57%), R: N (78%), S: N (57%), T: N (61%), V: D (63%), W: D (80%), Y: D (63%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: N, R: N, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Phenotypic and genetic spectrum of Danish patients... Ophthalmic Genet. 2012 Dec;33(4):225-31. doi: 10.3109/13816810.2011.643441. Epub 2012 Jan 9. Duno M, Schwartz M, Larsen PL, Rosenberg T
Phenotypic and genetic spectrum of Danish patients with ABCA4-related retinopathy.
Ophthalmic Genet. 2012 Dec;33(4):225-31. doi: 10.3109/13816810.2011.643441. Epub 2012 Jan 9., [PMID:22229821]

Abstract [show]
Background: Pathogenic variations in the ABCA4 gene were originally recognized as genetic background for the autosomal recessive disorders Stargardt disease and fundus flavimaculatus, but have expanded to embrace a diversity of retinal diseases, giving rise to the new diagnostic term, ABCA4-related retinopathy. Diagnostic genotyping of ABCA4 is complicated by the large size of the gene and the existence of approximately 600 known pathogenic variations, along with numerous rare polymorphisms. A commercial diagnostic array-based assay has been developed targeting known mutations, however a conclusive genetic diagnosis must rely on a comprehensive genetic screening as the mutation spectrum of ABCA4-related retinopathies continues to expand. Material and methods: Among 161 patients with a Stargardt-related phenotype previously assessed with the commercial ABCA4 mutation microarray, we analyzed the ABCA4 gene with High-resolution melting (HRM) in patients in whom the array analysis identified either a heterozygous mutation (n = 50) or no mutation (n = 30). Results: The HRM method detected each of the already known mutations and polymorphisms. We identified the second ABCA4 mutation in 31 of 50 heterozygous patients (62%). Several novel mutations were identified of which four were identified multiple times. The recurrent novel mutations were subsequently assessed among the 30 patients with possible ABCA4-related diseases, previously found to be negative for known ABCA4 mutations by array analysis. In total, 30 different mutations were identified of which 21 have not been described before. Conclusion: Scandinavian patients with ABCA4-related retinopathy appear to have a distinct mutation spectrum, which can be identified in patients of diverse clinical phenotypes.

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Sentences [show]
No. Sentence Comment
53 The c.6478 A>G (p.K2160E) mutation affects the second last base in the exon 47, which is highly conserved, and the mutation might therefore affect the donor splice site rather than the protein structure. Login to comment
58 [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.5584 + 1G>A na IVS39 New D188 c.5461-10T>C na IVS38 c.5693G>A p.R1898H 40 Known D433 c.5882G>A p.G1961E 42 c.6005 + 1G>A na IVS43 Known D134 c.4667 + 2G>T na IVS32 c.6098 T>G p.L2033R 44 New D186 c.3322C>T p.R1108C 22 c.6386 + 1G>A na IVS46 New D182 c.6089G>A p.R2030Q 44 c.6386 + 1G>A na IVS46 New D189 c.2894A>G p.N965S 19 c.6478 A>G p.K2160E 47 New *p.L541P and p.A1038V might be located on the same allele. Login to comment
66 Three of the four recurrent mutations were identified (p.L510R, c.2408delG and c.6386 + 1G>A), along with two mutations identified once during the initial HRM screen (p.G1127E, and p.K2160E). Login to comment
89 Encouraged by the result and the identification Table 2 Mutations identified by selected HRM screening of 30 patients without Asper-mutations Patient DNA Protein Exon/intron Ref D015 c.3380G>A p.G1127E 23 New* c.6478A>G p.K2160E 47 New* c.1654G>A p.V552I 12 29 D048 c.3765_3766dupTG na 25 New c.5693G>A p.R1898H 40 28 c.1964T>G p.F655C 14 30 D128 c.2408delG na 16 New* c.4243A>C p.T1415P 28 New D133 c.1529T>G p.L510R 11 New* c.6386 + 1G>A na 46 New* D061 c.1529T>G p.L510R 11 New* D102 c.2895T>G p.N965K 19 New D183 c.4069G>A p.A1357T 27 New D190 c.2408delG na 16 New* na; not applicable, *Identified during the initial mutation screen. Login to comment
97 Phenotype Patient Mutation 1 Mutation 2 Mutation 3 Stargardt-flavimaculatus D043 p.G863A p.P62S D050 p.G863A p.L510R D112 p.N965S p.L510R D069 p.A1038V p.L510R D099 p.R2030Q p.L510R D178 p.A1038V c.1843_1844delRG D166 p.G863A p.V767D D191 p.G863A p.A1357T D167 c.5461-10T>C p.R1368C D128 p.2408delG* p.T1415P D027 p.G863A c.4668-2A>G* D136 p.[L541P+A1038V] p.L1580S D048 c.3766dupTG* p.R1898H p.F655C D034 p.G863A c.4773 + 5G>A* D015 p. G1127K p.K2160E p.V552I D189 p.N965S p.K2160E D433 p.G1961E c.6005 + 1G>A* Generalized retinal dystrophy D117 c.3191-2A>G* c.2408delG* D135 p.N965S c.2408delG* D147 p.N965S c.2408delG* D173 p.C1490Y p.T972N D018 p.C2150Y p.L1246V D022 p.C1488R p.R1368C D108 p.G550R p.R1368C D414 p.G863A p.W1551X* D444 p.T901A c.4773 + 3A>G* D110 p.[L541P+A1038V] c.5584 + 1G>A* D182 p.R2030Q c.6386 + 1G>A* D186 p.R1108C c.6386 + 1G>AA* D133 p.L510R IVS46 + 1G>A* Cone-rod dystrophy D134 c.4667 + 2G>T* p.L2033R Atypical maculopathy D165 p.F608L p.C748Y D181 p.R2030Q p.G1127E D188 c.5461-10T>C p.R1898H *Predicted to compromise correct reading frame. Login to comment
105 In sample D015 the known p.V552I mutation was identified along with the newly identified p.K2160E and p.G1127E variations. Login to comment
106 In silico analysis with three different algorithms all predicted the clear pathogenic variations of p.G1127E and p.K2160E. Login to comment
109 The newly identified c.3766dupTG clearly disrupts the protein function and together with the known p.R1898H and p.F655C mutations confirm the diagnosis genetically. Login to comment
54 The c.6478 A>G (p.K2160E) mutation affects the second last base in the exon 47, which is highly conserved, and the mutation might therefore affect the donor splice site rather than the protein structure. Login to comment
60 [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.5584ߙ+ߙ1G>A na IVS39 New D188 c.5461-10T>C na IVS38 c.5693G>A p.R1898H 40 Known D433 c.5882G>A p.G1961E 42 c.6005ߙ+ߙ1G>A na IVS43 Known D134 c.4667ߙ+ߙ2G>T na IVS32 c.6098 T>G p.L2033R 44 New D186 c.3322C>T p.R1108C 22 c.6386ߙ+ߙ1G>A na IVS46 New D182 c.6089G>A p.R2030Q 44 c.6386ߙ+ߙ1G>A na IVS46 New D189 c.2894A>G p.N965S 19 c.6478 A>G p.K2160E 47 New *p.L541P and p.A1038V might be located on the same allele. Login to comment
68 Three of the four recurrent mutations were identified (p.L510R, c.2408delG and c.6386ߙ +ߙ 1G>A), along with two mutations identified once during the initial HRM screen (p.G1127E, and p.K2160E). Login to comment
91 Encouraged by the result and the identification Table 2ߒ Mutations identified by selected HRM screening of 30 patients without Asper-mutations Patient DNA Protein Exon/intron Ref D015 c.3380G>A p.G1127E 23 New* c.6478A>G p.K2160E 47 New* c.1654G>A p.V552I 12 29 D048 c.3765_3766dupTG na 25 New c.5693G>A p.R1898H 40 28 c.1964T>G p.F655C 14 30 D128 c.2408delG na 16 New* c.4243A>C p.T1415P 28 New D133 c.1529T>G p.L510R 11 New* c.6386ߙ+ߙ1G>A na 46 New* D061 c.1529T>G p.L510R 11 New* D102 c.2895T>G p.N965K 19 New D183 c.4069G>A p.A1357T 27 New D190 c.2408delG na 16 New* na; not applicable, *Identified during the initial mutation screen. Login to comment
100 Phenotype Patient Mutation 1 Mutation 2 Mutation 3 Stargardt-flavimaculatus D043 p.G863A p.P62S D050 p.G863A p.L510R D112 p.N965S p.L510R D069 p.A1038V p.L510R D099 p.R2030Q p.L510R D178 p.A1038V c.1843_1844delRG D166 p.G863A p.V767D D191 p.G863A p.A1357T D167 c.5461-10T>C p.R1368C D128 p.2408delG* p.T1415P D027 p.G863A c.4668-2A>G* D136 p.[L541P+A1038V] p.L1580S D048 c.3766dupTG* p.R1898H p.F655C D034 p.G863A c.4773ߙ+ߙ5G>A* D015 p. G1127K p.K2160E p.V552I D189 p.N965S p.K2160E D433 p.G1961E c.6005ߙ+ߙ1G>A* Generalized retinal dystrophy D117 c.3191-2A>G* c.2408delG* D135 p.N965S c.2408delG* D147 p.N965S c.2408delG* D173 p.C1490Y p.T972N D018 p.C2150Y p.L1246V D022 p.C1488R p.R1368C D108 p.G550R p.R1368C D414 p.G863A p.W1551X* D444 p.T901A c.4773ߙ+ߙ3A>G* D110 p.[L541P+A1038V] c.5584ߙ+ߙ1G>A* D182 p.R2030Q c.6386ߙ+ߙ1G>A* D186 p.R1108C c.6386ߙ+ߙ1G>AA* D133 p.L510R IVS46ߙ+ߙ1G>A* Cone-rod dystrophy D134 c.4667ߙ+ߙ2G>T* p.L2033R Atypical maculopathy D165 p.F608L p.C748Y D181 p.R2030Q p.G1127E D188 c.5461-10T>C p.R1898H *Predicted to compromise correct reading frame. Login to comment
108 In sample D015 the known p.V552I mutation was identified along with the newly identified p.K2160E and p.G1127E variations. Login to comment