UniProtKB/SwissProt variant VAR

Variant information

Variant position:

676

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Glycine (G) to Valine (V) at position 676 (G676V, p.Gly676Val).

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 glycine (G) to medium size and hydrophobic (V)

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

Involvement in disease:

Osteogenesis imperfecta 3 (OI3) [MIM:259420]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI3 is characterized by progressively deforming bones, very short stature, a triangular face, severe scoliosis, grayish sclera and dentinogenesis imperfecta. {ECO:0000269|PubMed:10408781, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:16879195, ECO:0000269|PubMed:1990009, ECO:0000269|PubMed:7520724, ECO:0000269|PubMed:7720740, ECO:0000269|PubMed:7749416, ECO:0000269|PubMed:7860070, ECO:0000269|PubMed:7881420, ECO:0000269|PubMed:8081394, ECO:0000269|PubMed:8444468, ECO:0000269|PubMed:8456807, ECO:0000269|PubMed:8723681, ECO:0000269|PubMed:8800927, ECO:0000269|PubMed:8829649}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:

Osteogenesis imperfecta 4 (OI4) [MIM:166220]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI4 is characterized by moderately short stature, mild to moderate scoliosis, grayish or white sclera and dentinogenesis imperfecta. {ECO:0000269|PubMed:1642148, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:16879195, ECO:0000269|PubMed:2052622, ECO:0000269|PubMed:2064612, ECO:0000269|PubMed:2897363, ECO:0000269|PubMed:7693712, ECO:0000269|PubMed:8094076, ECO:0000269|PubMed:8401517, ECO:0000269|PubMed:8800927}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In OI3 and OI4.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs66883877 [ dbSNP | Ensembl ]

Sequence information

Variant position:

676

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

Protein sequence length:

1366

The length of the canonical sequence.

Location on the sequence:

EKGEPGLRGEIGNPGRDGAR G APGAVGAPGPAGATGDRGEA

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                         EKGEPGLRGEIGNPGRDGARGAPGAVGAPGPAGATGDRGEA

                              EKGETGLRGEIGNPGRDGARGAPGAMGAPGPAGATGDRGEA

Mouse                         EKGETGLRGDTGNTGRDGARGIPGAVGAPGPAGASGDRGEA

Rat                           EKGETGLRGEIGNPGRDGARGAPGAIGAPGPAGASGDRGEA

Bovine                        EKGETGLRGDIGSPGRDGARGAPGAIGAPGPAGANGDRGEA

Chicken                       EKGAPGLRGDTGATGRDGARGLPGAIGAPGPAGGAGDRGEG

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	80 – 1119	Collagen alpha-2(I) chain

Literature citations

Severe (type III) osteogenesis imperfecta due to glycine substitutions in the central domain of the collagen triple helix.
Forlino A.; Zolezzi F.; Valli M.; Pignatti P.F.; Cetta G.; Brunelli P.C.; Mottes M.;
Hum. Mol. Genet. 3:2201-2206(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 663-746; VARIANT OI3 VAL-676;

Characterization of a type I collagen alpha 2(I) glycine-586 to valine substitution in osteogenesis imperfecta type IV. Detection of the mutation and prenatal diagnosis by a chemical cleavage method.
Bateman J.F.; Hannagan M.; Chan D.; Cole W.G.;
Biochem. J. 276:765-770(1991)
Cited for: VARIANT OI4 VAL-676;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08123: Variant p.Gly676Val