UniProtKB/Swiss-Prot P30531: Variant p.Tyr445Cys

Sodium- and chloride-dependent GABA transporter 1
Gene: SLC6A1
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Variant information Variant position:

445 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Tyrosine (Y) to Cysteine (C) at position 445 (Y445C, p.Tyr445Cys). 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 aromatic (Y) to medium size and polar (C) 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
Variant description:

Found in a patient with generalized epilepsy; uncertain significance; retains about 6% of wild-type GABA transporter activity. Any additional useful information about the variant.

Sequence information Variant position:

445 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

599 The length of the canonical sequence.
Location on the sequence:

AAVCIISYLIGLSNITQGGI Y VFKLFDYYSASGMSLLFLVF 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                         AAVCIISYLIGLSNITQGGIYVFKLFDYYSASGMSLLFLVF

Mouse                         AAVCIVSYLIGLSNITQGGIYVFKLFDYYSASGMSLLFLVF

Rat                           AAVCIVSYLIGLSNITQGGIYVFKLFDYYSASGMSLLFLVF

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 – 599	Sodium- and chloride-dependent GABA transporter 1
Topological domain	441 – 456	Extracellular
Helix	443 – 453

Literature citations
SLC6A1 variants identified in epilepsy patients reduce gamma-aminobutyric acid transport.
Mattison K.A.; Butler K.M.; Inglis G.A.S.; Dayan O.; Boussidan H.; Bhambhani V.; Philbrook B.; da Silva C.; Alexander J.J.; Kanner B.I.; Escayg A.;
Epilepsia 59:e135-e141(2018)
Cited for: VARIANTS GLU-94; ARG-235; CYS-445; 496-TRP--ILE-599 DEL AND ARG-550; VARIANTS MAE SER-270 AND ILE-272 DEL; CHARACTERIZATION OF VARIANTS GLU-94; ARG-235; CYS-445; 496-TRP--ILE-599 DEL AND ARG-550; CHARACTERIZATION OF VARIANTS MAE SER-270 AND ILE-272 DEL; FUNCTION; TRANSPORTER ACTIVITY;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.