UniProtKB/SwissProt variant VAR

Variant information

Variant position:

237

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 Arginine (R) to Glutamine (Q) at position 237 (R237Q, p.Arg237Gln).

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 (Q)

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

Involvement in disease:

Holt-Oram syndrome (HOS) [MIM:142900]: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects. {ECO:0000269|PubMed:10077612, ECO:0000269|PubMed:10842287, ECO:0000269|PubMed:12818525, ECO:0000269|PubMed:15735645, ECO:0000269|PubMed:20450920, ECO:0000269|PubMed:8988164, ECO:0000269|PubMed:8988165}. 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 HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894378 [ dbSNP | Ensembl ]

Sequence information

Variant position:

237

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

Protein sequence length:

518

The length of the canonical sequence.

Location on the sequence:

YQNHKITQLKIENNPFAKGF R GSDDMELHRMSRMQSKEYPV

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.

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 – 518	T-box transcription factor TBX5
DNA binding	58 – 238	T-box
Mutagenesis	234 – 234	K -> R. Does not affect acetylation of the protein.

Literature citations

Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.
Basson C.T.; Bachinsky D.R.; Lin R.C.; Levi T.; Elkins J.A.; Soults J.; Grayzel D.; Kroumpouzou E.; Traill T.A.; Leblanc-Straceski J.; Renault B.; Kucherlapati R.; Seidman J.G.; Seidman C.E.;
Nat. Genet. 15:30-35(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); ALTERNATIVE SPLICING; VARIANT HOS GLN-237;

Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.
Basson C.T.; Huang T.; Lin R.C.; Bachinksy D.R.; Weremowicz S.; Vaglio A.; Bruzzone R.; Quadrelli R.; Lerone M.; Romeo G.; Silengo M.; Pereira A.; Krieger J.; Mesquita S.F.; Kamisago M.; Morton C.C.; Pierpont M.E.M.; Muller C.W.; Seidman J.G.; Seidman C.E.;
Proc. Natl. Acad. Sci. U.S.A. 96:2919-2924(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS HOS ARG-80; GLN-237 AND TRP-237;

Mutation in myosin heavy chain 6 causes atrial septal defect.
Ching Y.-H.; Ghosh T.K.; Cross S.J.; Packham E.A.; Honeyman L.; Loughna S.; Robinson T.E.; Dearlove A.M.; Ribas G.; Bonser A.J.; Thomas N.R.; Scotter A.J.; Caves L.S.D.; Tyrrell G.P.; Newbury-Ecob R.A.; Munnich A.; Bonnet D.; Brook J.D.;
Nat. Genet. 37:423-428(2005)
Cited for: CHARACTERIZATION OF VARIANT HOS GLN-237;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99593: Variant p.Arg237Gln