Variant information:

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Variant position: 248

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

Type of variant: Disease [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.]

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

• Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
• Polymorphism: No disease-association has been reported.
• Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change: From Glycine (G) to Valine (V) at position 248 (G248V, p.Gly248Val).

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: Defects in TBX4 are the cause of small patella syndrome (SPS) [MIM:147891]; also known as ischiopatellar dysplasia or Scott-Taor syndrome. SPS is an autosomal dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami.

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 SPS.

Any additional useful information about the variant.

Other resources: 

Links to websites of interest for the variant.

• GeneReviews
• Variant rs28938474 [ dbSNP | Ensembl ]

Sequence information:

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Variant position: 248

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

Protein sequence length: 545

The length of the canonical sequence.

Location on the sequence:  TSYQNHKITQLKIENNPFAK  G FRGSDDSDLRVARLQSKEYP

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                         TSYQNHKITQLKIENNPFAKGFRGSDDSDLRVARLQSKEYP

Mouse                         TSYQNHKITQLKIENNPFAKGFRGSDDSDLRVARLQSKEYP

Dog                           TSYQNHKITQLKIENNPFAKGFRGSDDSDLRVARLQSKEYP

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	1 – 545	T-box transcription factor TBX4
DNA binding	71 – 251	T-box

Literature citations

Mutations in the human TBX4 gene cause small patella syndrome.
Bongers E.M.H.F.; Duijf P.H.G.; van Beersum S.E.M.; Schoots J.; van Kampen A.; Burckhardt A.; Hamel B.C.J.; Losan F.; Hoefsloot L.H.; Yntema H.G.; Knoers N.V.A.M.; van Bokhoven H.;
Am. J. Hum. Genet. 74:1239-1248(2004)
Cited for: VARIANTS SPS VAL-248 AND ARG-531; VARIANTS ALA-6 AND VAL-35;