UniProtKB/SwissProt variant VAR

Variant information

Variant position:

710

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 Alanine (A) to Valine (V) at position 710 (A710V, p.Ala710Val).

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 small size and hydrophobic (A) to medium size and hydrophobic (V)

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

BLOSUM score:

0

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 VSCN2; almost complete loss of ERBB2 and ERBB3 phosphorylation in the presence or in the absence of NRG1 stimulation, suggesting alteration of downstream signaling; does not affect the subcellular localization at the cell membrane.

Any additional useful information about the variant.

Sequence information

Variant position:

710

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

Protein sequence length:

1255

The length of the canonical sequence.

Location on the sequence:

LLQETELVEPLTPSGAMPNQ A QMRILKETELRKVKVLGSGA

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                         LLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGA

                              LLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGA

Mouse                         LLQETELVEPLTPSGAVPNQAQMRILKETELRKLKVLGSGA

Rat                           LLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGA

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	23 – 1255	Receptor tyrosine-protein kinase erbB-2
Topological domain	676 – 1255	Cytoplasmic
Mutagenesis	706 – 706	M -> A. No effect on isoform production.
Mutagenesis	712 – 712	M -> A. No effect on isoform production.

Literature citations

Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans.
Le T.L.; Galmiche L.; Levy J.; Suwannarat P.; Hellebrekers D.M.; Morarach K.; Boismoreau F.; Theunissen T.E.; Lefebvre M.; Pelet A.; Martinovic J.; Gelot A.; Guimiot F.; Calleroz A.; Gitiaux C.; Hully M.; Goulet O.; Chardot C.; Drunat S.; Capri Y.; Bole-Feysot C.; Nitschke P.; Whalen S.; Mouthon L.; Babcock H.E.; Hofstra R.; de Coo I.F.; Tabet A.C.; Molina T.J.; Keren B.; Brooks A.; Smeets H.J.; Marklund U.; Gordon C.T.; Lyonnet S.; Amiel J.; Bondurand N.;
J. Clin. Invest. 131:0-0(2021)
Cited for: INVOLVEMENT IN VSCN2; VARIANT VSCN2 VAL-710; CHARACTERIZATION OF VARIANT VSCN2 VAL-710; SUBCELLULAR LOCATION; PHOSPHORYLATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04626: Variant p.Ala710Val