UniProtKB/Swiss-Prot O00555: Variant p.Glu992Val

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 992 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Glutamate (E) to Valine (V) at position 992 (E992V, p.Glu992Val). 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 medium size and acidic (E) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -2 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
Polymorphism: The poly-Gln region of CACNA1A is polymorphic: 6 to 17 repeats in the normal population, expanded to about 21 to 30 repeats in SCA6. Repeat expansion has been reported also in a EA2 family. Additional information on the polymorphism described.
Other resources: Links to websites of interest for the variant.

• Variant rs16023 [ dbSNP | Ensembl ]

Sequence information

Variant position: 992 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 2506 The length of the canonical sequence.
Location on the sequence: KAERRARHREGSRPARGGEG E GEGPDGGERRRRHRHGAPAT 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 – 2506	Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Topological domain	714 – 1241	Cytoplasmic
Region	818 – 1220	Disordered

Literature citations

Genetic heterogeneity in Italian families with familial hemiplegic migraine.
Carrera P.; Piatti M.; Stenirri S.; Grimaldi L.M.; Marchioni E.; Curcio M.; Righetti P.G.; Ferrari M.; Gelfi C.;
Neurology 53:26-33(1999)
Cited for: VARIANT VAL-992; VARIANT FHM1 LEU-1455; Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4.
von Brevern M.; Ta N.; Shankar A.; Wiste A.; Siegel A.; Radtke A.; Sander T.; Escayg A.;
Headache 46:1136-1141(2006)
Cited for: VARIANTS ASP-917; VAL-992 AND SER-1104; The interplay of two single nucleotide polymorphisms in the CACNA1A gene may contribute to migraine susceptibility.
D'Onofrio M.; Ambrosini A.; Di Mambro A.; Arisi I.; Santorelli F.M.; Grieco G.S.; Nicoletti F.; Nappi G.; Pierelli F.; Schoenen J.; Buzzi M.G.;
Neurosci. Lett. 453:12-15(2009)
Cited for: VARIANTS ASP-917 AND VAL-992;