UniProtKB/SwissProt variant VAR

Variant information

Variant position:

4115

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 Arginine (R) to Cysteine (C) at position 4115 (R4115C, p.Arg4115Cys).

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 large size and basic (R) to medium size and polar (C)

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

BLOSUM score:

-3

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 USH2A and RP39; associated with M-4425.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs111033275 [ dbSNP | Ensembl ]

Sequence information

Variant position:

4115

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

5202

The length of the canonical sequence.

Location on the sequence:

GVIKTYNIFSDGFLEYSGLN R QFLFRRLDPFTLYTLTLEAC

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                         GVIKTYNIFSDGFLEYSGLNRQFLFRRLDPFTLYTLTLEAC

Mouse                         GVIKAYNIFNDGVLEYSGLGRQFLFRRLAPFTLYTLILEAC

Rat                           GVIKAYNVFSDGLPEYSGLGRQFLFRRLAPFTLYILTLEAC

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	32 – 5202	Usherin
Topological domain	32 – 5042	Extracellular
Domain	4068 – 4153	Fibronectin type-III 26
Alternative sequence	1547 – 5202	Missing. In isoform 2.

Literature citations

Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.
Van Wijk E.; Pennings R.J.E.; Te Brinke H.; Claassen A.; Yntema H.G.; Hoefsloot L.H.; Cremers F.P.M.; Cremers C.W.R.J.; Kremer H.;
Am. J. Hum. Genet. 74:738-744(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); TISSUE SPECIFICITY; VARIANTS USH2A CYS-4115 AND MET-4425;

Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.
Baux D.; Larrieu L.; Blanchet C.; Hamel C.; Ben Salah S.; Vielle A.; Gilbert-Dussardier B.; Holder M.; Calvas P.; Philip N.; Edery P.; Bonneau D.; Claustres M.; Malcolm S.; Roux A.-F.;
Hum. Mutat. 28:781-789(2007)
Cited for: VARIANTS USH2A GLU-218; PHE-280; LYS-284; TRP-334; GLN-334; HIS-346; ILE-352; PHE-759; GLU-1833; SER-2795; ARG-3282; MET-3571; GLU-3895; MET-3976; CYS-4115 AND MET-4425; VARIANT PHE-1572;

Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II.
Dreyer B.; Brox V.; Tranebjaerg L.; Rosenberg T.; Sadeghi A.M.; Moeller C.; Nilssen O.;
Hum. Mutat. 29:451-451(2008)
Cited for: VARIANTS USH2A TYR-163; ARG-268; CYS-303; TRP-334; HIS-346; ILE-352; ARG-536; PHE-759; LEU-1212; ASP-2265-ASP-TYR-2266 DELINS ASP; GLY-3124; THR-3504; ARG-3521; ILE-4054; ARG-4232; ILE-4439; CYS-4487; HIS-4592 AND ARG-4795; VARIANTS THR-125; MET-230; ASP-478; SER-595; VAL-644; ARG-713; PRO-1349; LYS-1486; PHE-1572; THR-1665; CYS-1757; ASN-2080; ASN-2086; THR-2106; THR-2169; ALA-2238; HIS-2292; ALA-2562; GLN-2875; PHE-2886; LYS-3088; SER-3099; ALA-3115; ASN-3144; ASP-3199; ALA-3411; LEU-3590; ILE-3835; VAL-3868; THR-3893; CYS-4115; LEU-4433; VAL-4624 AND TRP-5031;

Next-generation genetic testing for retinitis pigmentosa.
Neveling K.; Collin R.W.; Gilissen C.; van Huet R.A.; Visser L.; Kwint M.P.; Gijsen S.J.; Zonneveld M.N.; Wieskamp N.; de Ligt J.; Siemiatkowska A.M.; Hoefsloot L.H.; Buckley M.F.; Kellner U.; Branham K.E.; den Hollander A.I.; Hoischen A.; Hoyng C.; Klevering B.J.; van den Born L.I.; Veltman J.A.; Cremers F.P.; Scheffer H.;
Hum. Mutat. 33:963-972(2012)
Cited for: VARIANTS RP39 PHE-419; PHE-759; CYS-1859; HIS-2460; TYR-3358; ARG-3669; CYS-4115; HIS-4192 AND MET-4425;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75445: Variant p.Arg4115Cys