UniProtKB/SwissProt variant VAR

Variant information

Variant position:

178

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 Cysteine (C) at position 178 (R178C, p.Arg178Cys).

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 (C)

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

Variant description:

In MMIHS5; interferes with proper polymerization into thin filaments leading to impaired contractility of the smooth muscle.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs78001248 [ dbSNP | Ensembl ]

Sequence information

Variant position:

178

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

Protein sequence length:

376

The length of the canonical sequence.

Location on the sequence:

DGVTHNVPIYEGYALPHAIM R LDLAGRDLTDYLMKILTERG

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                         DGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERG

Mouse                         DGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERG

Rat                           DGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERG

Bovine                        DGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERG

Chicken                       DGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERG

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	2 – 376	Actin, gamma-enteric smooth muscle, intermediate form
Chain	3 – 376	Actin, gamma-enteric smooth muscle

Literature citations

De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis.
Thorson W.; Diaz-Horta O.; Foster J. II; Spiliopoulos M.; Quintero R.; Farooq A.; Blanton S.; Tekin M.;
Hum. Genet. 133:737-742(2014)
Cited for: VARIANTS MMIHS5 CYS-178 AND LEU-178; CHARACTERIZATION OF VARIANTS MMIHS5 CYS-178 AND LEU-178; INVOLVEMENT IN MMIHS5;

Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome.
Wangler M.F.; Gonzaga-Jauregui C.; Gambin T.; Penney S.; Moss T.; Chopra A.; Probst F.J.; Xia F.; Yang Y.; Werlin S.; Eglite I.; Kornejeva L.; Bacino C.A.; Baldridge D.; Neul J.; Lehman E.L.; Larson A.; Beuten J.; Muzny D.M.; Jhangiani S.; Gibbs R.A.; Lupski J.R.; Beaudet A.;
PLoS Genet. 10:E1004258-E1004258(2014)
Cited for: VARIANTS MMIHS5 CYS-40; HIS-40; ASN-134; CYS-178; HIS-178 AND CYS-257; VARIANTS VSCM1 HIS-40; THR-45; GLY-63; LEU-110 AND ASP-198; INVOLVEMENT IN MMIHS5; INVOLVEMENT IN VSCM1;

Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.
Moreno C.A.; Metze K.; Lomazi E.A.; Bertola D.R.; Barbosa R.H.; Cosentino V.; Sobreira N.; Cavalcanti D.P.;
Am. J. Med. Genet. A 170:2965-2974(2016)
Cited for: VARIANTS MMIHS5 CYS-178; LEU-178 AND HIS-257; VARIANT VSCM1 ILE-195; INVOLVEMENT IN MMIHS5; INVOLVEMENT IN VSCM1;

ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.
Halim D.; Hofstra R.M.; Signorile L.; Verdijk R.M.; van der Werf C.S.; Sribudiani Y.; Brouwer R.W.; van Ijcken W.F.; Dahl N.; Verheij J.B.; Baumann C.; Kerner J.; van Bever Y.; Galjart N.; Wijnen R.M.; Tibboel D.; Burns A.J.; Muller F.; Brooks A.S.; Alves M.M.;
Hum. Mol. Genet. 25:571-583(2016)
Cited for: VARIANTS MMIHS5 CYS-40; GLN-63; CYS-178; HIS-178 AND LEU-178; INVOLVEMENT IN MMIHS5; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS MMIHS5 CYS-40; GLN-63; CYS-178; HIS-178 AND LEU-178; CHARACTERIZATION OF VARIANT VSCM1 SER-148;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P63267: Variant p.Arg178Cys