Variant position:  948

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Cysteine (C) to Tyrosine (Y) at position 948 (C948Y, p.Cys948Tyr).

Physico-chemical properties:  Change from medium size and polar (C) to large size and aromatic (Y)

BLOSUM score:  -2

Variant description:  In RP12 and LCA8; without preservation of the paraarteriolar retinal pigment epithelium.

Other resources:  

• Variant rs62645748 [ dbSNP | Ensembl ]

Variant position:  948

Protein sequence length:  1406

Location on the sequence:   CGFSPCPHGAQCQPVLQGFE  C IANAVFNGQSGQILFRSNGN

Residue conservation: 

Human                         CGFSPCPHGAQCQPVLQGFECIANAVFNGQSGQILFRSNGN

Mouse                         CQLSPCPPTAECQLLPQGFECIANAVFSGLSREILFRSNGN

Sequence annotation in neighborhood:  

Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).
den Hollander A.I.; ten Brink J.B.; de Kok Y.J.M.; van Soest S.; van den Born L.I.; van Driel M.A.; van de Pol D.J.R.; Payne A.M.; Bhattacharya S.S.; Kellner U.; Hoyng C.B.; Westerveld A.; Brunner H.G.; Bleeker-Wagemakers E.M.; Deutman A.F.; Heckenlively J.R.; Cremers F.P.M.; Bergen A.A.B.;
Nat. Genet. 23:217-221(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); VARIANTS RP12 VAL-161; TRP-250; MET-745; CYS-764; TYR-948; THR-1041 AND PRO-1071;

Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene.
den Hollander A.I.; Heckenlively J.R.; van den Born L.I.; de Kok Y.J.M.; van der Velde-Visser S.D.; Kellner U.; Jurklies B.; van Schooneveld M.J.; Blankenagel A.; Rohrschneider K.; Wissinger B.; Cruysberg J.R.M.; Deutman A.F.; Brunner H.G.; Apfelstedt-Sylla E.; Hoyng C.B.; Cremers F.P.M.;
Am. J. Hum. Genet. 69:198-203(2001)
Cited for: VARIANTS LCA8 TYR-948 AND ARG-1100; VARIANTS RP12 CYS-433; CYS-764; HIS-837; TYR-948; ARG-1181 AND THR-1354; VARIANTS MET-289; MET-821; SER-894 AND HIS-1331;

Mutations in the CRB1 gene cause Leber congenital amaurosis.
Lotery A.J.; Jacobson S.G.; Fishman G.A.; Weleber R.G.; Fulton A.B.; Namperumalsamy P.; Heon E.; Levin A.V.; Grover S.; Rosenow J.R.; Kopp K.K.; Sheffield V.C.; Stone E.M.;
Arch. Ophthalmol. 119:415-420(2001)
Cited for: VARIANTS LCA8 VAL-144; TYR-383; GLY-480; ARG-480; TYR-681; CYS-764; TYR-948; ARG-1205 AND HIS-1317; VARIANTS MET-289; GLN-769 AND HIS-1331;

Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination.
Jacobson S.G.; Cideciyan A.V.; Aleman T.S.; Pianta M.J.; Sumaroka A.; Schwartz S.B.; Smilko E.E.; Milam A.H.; Sheffield V.C.; Stone E.M.;
Hum. Mol. Genet. 12:1073-1078(2003)
Cited for: VARIANTS LCA8 SER-749 DEL; CYS-764; TYR-948 AND PHE-1218;

Study of the involvement of the RGR, CRPB1, and CRB1 genes in the pathogenesis of autosomal recessive retinitis pigmentosa.
Bernal S.; Calaf M.; Garcia-Hoyos M.; Garcia-Sandoval B.; Rosell J.; Adan A.; Ayuso C.; Baiget M.;
J. Med. Genet. 40:E89-E89(2003)
Cited for: VARIANTS RP12 SER-749 DEL; GLY-891; TYR-948; LEU-962 DEL AND THR-1100; VARIANT LCA8 THR-205; VARIANTS MET-289; GLU-679; HIS-769 AND HIS-1331;

Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.
Hanein S.; Perrault I.; Gerber S.; Tanguy G.; Barbet F.; Ducroq D.; Calvas P.; Dollfus H.; Hamel C.; Lopponen T.; Munier F.; Santos L.; Shalev S.; Zafeiriou D.; Dufier J.-L.; Munnich A.; Rozet J.-M.; Kaplan J.;
Hum. Mutat. 23:306-317(2004)
Cited for: VARIANTS LCA8 TYR-584; GLN-710; THR-741; MET-745; CYS-764; THR-852; TYR-948; ILE-1025; ARG-1103; ARG-1107; PRO-1107 AND SER-1321;

CRB1 mutation spectrum in inherited retinal dystrophies.
den Hollander A.I.; Davis J.; van der Velde-Visser S.D.; Zonneveld M.N.; Pierrottet C.O.; Koenekoop R.K.; Kellner U.; van den Born L.I.; Heckenlively J.R.; Hoyng C.B.; Handford P.A.; Roepman R.; Cremers F.P.M.;
Hum. Mutat. 24:355-369(2004)
Cited for: VARIANTS RP12 PHE-195; GLU-578; TYR-587; MET-745; CYS-764; THR-836; SER-850; TYR-948; SER-959; ILE-986; THR-1100 AND HIS-1383; VARIANT LCA8 THR-205; VARIANT GLN-905;

Clinical phenotypes in carriers of Leber congenital amaurosis mutations.
Galvin J.A.; Fishman G.A.; Stone E.M.; Koenekoop R.K.;
Ophthalmology 112:349-356(2005)
Cited for: VARIANTS LCA8 PRO-753; CYS-764 AND TYR-948;

Evaluation of genotype-phenotype associations in Leber congenital amaurosis.
Galvin J.A.; Fishman G.A.; Stone E.M.; Koenekoop R.K.;
Retina 25:919-929(2005)
Cited for: VARIANTS LCA8 ARG-480; TYR-681; PRO-753; CYS-764 AND TYR-948; VARIANT SER-488;

Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays.
den Hollander A.I.; Lopez I.; Yzer S.; Zonneveld M.N.; Janssen I.M.; Strom T.M.; Hehir-Kwa J.Y.; Veltman J.A.; Arends M.L.; Meitinger T.; Musarella M.A.; van den Born L.I.; Fishman G.A.; Maumenee I.H.; Rohrschneider K.; Cremers F.P.; Koenekoop R.K.;
Invest. Ophthalmol. Vis. Sci. 48:5690-5698(2007)
Cited for: VARIANTS LCA8 TYR-939; TYR-948 AND PHE-1332;

Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes.
Coppieters F.; Casteels I.; Meire F.; De Jaegere S.; Hooghe S.; van Regemorter N.; Van Esch H.; Matuleviciene A.; Nunes L.; Meersschaut V.; Walraedt S.; Standaert L.; Coucke P.; Hoeben H.; Kroes H.Y.; Vande Walle J.; de Ravel T.; Leroy B.P.; De Baere E.;
Hum. Mutat. 31:E1709-E1766(2010)
Cited for: INVOLVEMENT IN RETINAL DYSTROPHIES; VARIANTS EARLY-ONSET RETINAL DYSTROPHY TYR-310; CYS-764 AND TYR-948; VARIANT VAL-491;

Development of a diagnostic genetic test for simplex and autosomal recessive retinitis pigmentosa.
Clark G.R.; Crowe P.; Muszynska D.; O'Prey D.; O'Neill J.; Alexander S.; Willoughby C.E.; McKay G.J.; Silvestri G.; Simpson D.A.;
Ophthalmology 117:2169-2177(2010)
Cited for: VARIANTS RP12 TRP-45; VAL-710; MET-745; SER-850; ILE-901; TYR-948 AND HIS-1383; VARIANT HIS-769;

Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1.
Henderson R.H.; Mackay D.S.; Li Z.; Moradi P.; Sergouniotis P.; Russell-Eggitt I.; Thompson D.A.; Robson A.G.; Holder G.E.; Webster A.R.; Moore A.T.;
Br. J. Ophthalmol. 95:811-817(2011)
Cited for: VARIANTS RP12 SER-157; TRP-250; LYS-312; CYS-675; VAL-710; MET-745; CYS-764; THR-836; ARG-846; TYR-948; SER-1012; ASN-1025 AND GLY-1174; VARIANTS LCA8 THR-205; SER-850; THR-1003; ARG-1103; PRO-1107; GLY-1174 AND LEU-1381; VARIANTS EARLY-ONSET RETINAL DYSTROPHY THR-741 AND ASP-1365;

CRB1 mutations in inherited retinal dystrophies.
Bujakowska K.; Audo I.; Mohand-Said S.; Lancelot M.E.; Antonio A.; Germain A.; Leveillard T.; Letexier M.; Saraiva J.P.; Lonjou C.; Carpentier W.; Sahel J.A.; Bhattacharya S.S.; Zeitz C.;
Hum. Mutat. 33:306-315(2012)
Cited for: INVOLVEMENT IN RETINAL DYSTROPHIES; VARIANTS RP12 TYR-584; PHE-740; THR-741; THR-836; TYR-948 AND ARG-1103; VARIANTS EARLY-ONSET RETINAL DYSTROPHY ASN-789 DEL; CYS-1198 AND SER-1223;

The correlation between CRB1 variants and the clinical severity of Brazilian patients with different inherited retinal dystrophy phenotypes.
Motta F.L.; Salles M.V.; Costa K.A.; Filippelli-Silva R.; Martin R.P.; Sallum J.M.F.;
Sci. Rep. 7:8654-8654(2017)
Cited for: INVOLVEMENT IN RETINAL DYSTROPHIES; VARIANTS LCA8 328-TRP--ILE-1406 DEL; ARG-948; TYR-948 AND 1226-GLY--ILE-1406 DEL; VARIANTS EARLY-ONSET RETINAL DYSTROPHY HIS-764 AND 1390-ARG--ILE-1406 DEL; VARIANTS RP12 THR-836 AND ARG-1107; VARIANTS PRO-479; PRO-921 AND ASN-1031;