UniProtKB/SwissProt variant VAR

Variant information

Variant position:

741

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 Methionine (M) to Threonine (T) at position 741 (M741T, p.Met741Thr).

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 hydrophobic (M) to medium size and polar (T)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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 LCA8; also found in patients with early-onset rod-cone retinal dystrophy.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs62636267 [ dbSNP | Ensembl ]

Sequence information

Variant position:

741

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:

STGYVIFTLDESYGDTISLS M FVRTLQPSGLLLALENSTYQ

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                         STGYVIFTLDESYGDTISLSMFVRTLQPSGLLLALENSTYQ

Mouse                         STGYAAFSVNDNYGQNFSLSMFVRTRQPLGLLLALENSTYQ

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	714 – 885	Laminin G-like 2
Glycosylation	757 – 757	N-linked (GlcNAc...) asparagine
Alternative sequence	710 – 1245	Missing. In isoform 5.

Literature citations

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;

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;

Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis.
Li L.; Xiao X.; Li S.; Jia X.; Wang P.; Guo X.; Jiao X.; Zhang Q.; Hejtmancik J.F.;
PLoS ONE 6:E19458-E19458(2011)
Cited for: VARIANTS LCA8 PRO-635 AND THR-741; VARIANTS LYS-222 AND MET-289;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P82279: Variant p.Met741Thr