UniProtKB/SwissProt variant VAR

Variant information

Variant position:

2

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 Alanine (A) to Glycine (G) at position 2 (A2G, p.Ala2Gly).

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 glycine (G)

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

Involvement in disease:

Spinal muscular atrophy 3 (SMA3) [MIM:253400]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. 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.

Involvement in disease:

Spinal muscular atrophy 2 (SMA2) [MIM:253550]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. {ECO:0000269|PubMed:10732802, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. 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 SMA2 and SMA3.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs75030631 [ dbSNP | Ensembl ]

Sequence information

Variant position:

2

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

Protein sequence length:

294

The length of the canonical sequence.

Location on the sequence:

M A MSSGGSGGGVPEQEDSVLFR

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                         MAMSSGGSGGGVPEQEDSVLFR

                              -----MGGGGGLPEPEDSVLFR

Mouse                         MAM---GSGGAGSEQEDTVLFR

Rat                           MAM--GSGGGAGSEQEDTVLFR

Bovine                        ----MGGGGGGFPEPEDSVLFR

Cat                           MAM---GGGSGVPEQEDSVLFR

Drosophila                    ----------------------

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
Initiator methionine	1 – 1	Removed
Chain	2 – 294	Survival motor neuron protein
Modified residue	2 – 2	N-acetylalanine
Modified residue	4 – 4	Phosphoserine; by PKA
Modified residue	5 – 5	Phosphoserine; by PKA
Modified residue	8 – 8	Phosphoserine; by PKA

Literature citations

Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.
Parsons D.W.; McAndrew P.E.; Iannaccone S.T.; Mendell J.R.; Burghes A.H.; Prior T.W.;
Am. J. Hum. Genet. 63:1712-1723(1998)
Cited for: VARIANT SMA2/SMA3 GLY-2; VARIANT SMA3 SER-275;

Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy.
Sun Y.; Grimmler M.; Schwarzer V.; Schoenen F.; Fischer U.; Wirth B.;
Hum. Mutat. 25:64-71(2005)
Cited for: VARIANTS SMA1/SMA2/SMA3 ASN-30; VAL-44; ARG-95; GLY-111; GLY-262; CYS-272 AND ILE-274; CHARACTERIZATION OF VARIANTS SMA1/SMA2/SMA3 ASN-30; VAL-44; ARG-95 AND GLY-111;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q16637: Variant p.Ala2Gly