UniProtKB/Swiss-Prot P82279: Variant p.Cys948Tyr

Protein crumbs homolog 1
Gene: CRB1
Feedback?

Variant information Variant position:

948 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Cysteine (C) to Tyrosine (Y) at position 948 (C948Y, p.Cys948Tyr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and polar (C) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In RP12 and LCA8; without preservation of the paraarteriolar retinal pigment epithelium. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs62645748 [ dbSNP | Ensembl ]

Sequence information Variant position:

948 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1406 The length of the canonical sequence.
Location on the sequence:

CGFSPCPHGAQCQPVLQGFE C IANAVFNGQSGQILFRSNGN The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         CGFSPCPHGAQCQPVLQGFECIANAVFNGQSGQILFRSNGN

Mouse                         CQLSPCPPTAECQLLPQGFECIANAVFSGLSREILFRSNGN

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	26 – 1406	Protein crumbs homolog 1
Topological domain	26 – 1347	Extracellular
Domain	924 – 960	EGF-like 14
Glycosylation	968 – 968	N-linked (GlcNAc...) asparagine
Disulfide bond	933 – 948
Alternative sequence	710 – 1245	Missing. In isoform 5.

Literature citations
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;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.