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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35523: Variant p.Arg496Ser

Chloride channel protein 1
Gene: CLCN1
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Variant information Variant position: help 496 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Serine (S) at position 496 (R496S, p.Arg496Ser). 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: help Change from large size and basic (R) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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: help In MCAR; loss of chloride channel activity; recessive. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 496 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 988 The length of the canonical sequence.
Location on the sequence: help TMPIPCGGFMPVFVLGAAFG R LVGEIMAMLFPDGILFDDII 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPDGILFDDII

                              TMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPDGILFDDII

Mouse                         TMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPEGILFDDII

Rat                           TMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPEGILFDDII
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 988 Chloride channel protein 1
Transmembrane 479 – 498 Helical
Binding site 484 – 484
Mutagenesis 496 – 496 R -> K. Changed gating of the channel.
Mutagenesis 499 – 499 G -> KE. Changed gating of the channel.
Mutagenesis 499 – 499 G -> Q. No effect on gating of the channel.
Mutagenesis 500 – 500 E -> Q. No effect on channel function.
Helix 484 – 502



Literature citations
Genomic organization of the human muscle chloride channel ClC-1 and analysis of novel mutations leading to Becker-type myotonia.
Lorenz C.; Meyer-Kleine C.; Steinmeyer K.; Koch M.C.; Jentsch T.J.;
Hum. Mol. Genet. 3:941-946(1994)
Cited for: VARIANTS MCAR ILE-327; CYS-413 AND SER-496; CHARACTERIZATION OF VARIANTS MCAR ILE-327 AND SER-496; FUNCTION; Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations.
Ronstedt K.; Sternberg D.; Detro-Dassen S.; Gramkow T.; Begemann B.; Becher T.; Kilian P.; Grieschat M.; Machtens J.P.; Schmalzing G.; Fischer M.; Fahlke C.;
Sci. Rep. 5:15382-15382(2015)
Cited for: VARIANTS MCAR ARG-43; LEU-70; ASP-137; HIS-160; SER-496 AND GLU-855; CHARACTERIZATION OF VARIANTS MCAR ARG-43; LEU-70; ASP-137 AND HIS-160; FUNCTION; SUBCELLULAR LOCATION; SUBUNIT;
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.