UniProtKB/SwissProt variant VAR

Variant information

Variant position:

576

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 Glutamine (Q) at position 576 (R576Q, p.Arg576Gln).

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

Variant description:

In PTHS; loss of function.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121909121 [ dbSNP | Ensembl ]

Sequence information

Variant position:

576

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

Protein sequence length:

667

The length of the canonical sequence.

Location on the sequence:

EQKAEREKERRMANNARERL R VRDINEAFKELGRMVQLHLK

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                         EQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLK

                              EQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLK

Mouse                         EQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLK

Rat                           EQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLK

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 – 667	Transcription factor 4
Domain	564 – 617	bHLH
Helix	565 – 594

Literature citations

Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction.
Amiel J.; Rio M.; de Pontual L.; Redon R.; Malan V.; Boddaert N.; Plouin P.; Carter N.P.; Lyonnet S.; Munnich A.; Colleaux L.;
Am. J. Hum. Genet. 80:988-993(2007)
Cited for: VARIANTS PTHS TRP-576 AND GLN-576;

Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome.
de Pontual L.; Mathieu Y.; Golzio C.; Rio M.; Malan V.; Boddaert N.; Soufflet C.; Picard C.; Durandy A.; Dobbie A.; Heron D.; Isidor B.; Motte J.; Newburry-Ecob R.; Pasquier L.; Tardieu M.; Viot G.; Jaubert F.; Munnich A.; Colleaux L.; Vekemans M.; Etchevers H.; Lyonnet S.; Amiel J.;
Hum. Mutat. 30:669-676(2009)
Cited for: VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610; CHARACTERIZATION OF VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610;

Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum.
Whalen S.; Heron D.; Gaillon T.; Moldovan O.; Rossi M.; Devillard F.; Giuliano F.; Soares G.; Mathieu-Dramard M.; Afenjar A.; Charles P.; Mignot C.; Burglen L.; Van Maldergem L.; Piard J.; Aftimos S.; Mancini G.; Dias P.; Philip N.; Goldenberg A.; Le Merrer M.; Rio M.; Josifova D.; Van Hagen J.M.; Lacombe D.; Edery P.; Dupuis-Girod S.; Putoux A.; Sanlaville D.; Fischer R.; Drevillon L.; Briand-Suleau A.; Metay C.; Goossens M.; Amiel J.; Jacquette A.; Giurgea I.;
Hum. Mutat. 33:64-72(2012)
Cited for: VARIANTS PTHS TRP-565; GLY-572; GLN-572; HIS-574; PRO-574; TRP-576; GLN-576; PRO-578; PRO-583 AND VAL-610;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P15884: Variant p.Arg576Gln