UniProtKB/Swiss-Prot O60741: Variant p.Pro851Ala

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Gene: HCN1
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Variant information Variant position:

851 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 Proline (P) to Alanine (A) at position 851 (P851A, p.Pro851Ala). 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 hydrophobic (P) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

Found in a patient with sinus bradychardia; uncertain significance; affects channel properties as it results in a negative shift in the threshold voltage of activation and slower activation kinetics compared to the wild-type. Any additional useful information about the variant.

Sequence information Variant position:

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

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

GRSTVPQRVTLFRQMSSGAI P PNRGVPPAPPPPAAALPRES 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                         GRSTVPQRVTLFRQMSSGAIPPNRGVPPAPPPPAAALPRES

Mouse                         SRSTVPQRVTLFRQMSSGAIPPNRGVPPAPPPPAA-VQRES

Rat                           SRSTVPQRVTLFRQMSSGAIPPNRGVPPAPPPPAA-VQRES

Rabbit                        GRSTVPQRVTLFRQMSSGAIPPNRGVPPAPPPPAAPLQREA

Fission yeast                 -----------------------------------------

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 – 890	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Topological domain	393 – 890	Cytoplasmic
Region	845 – 890	Disordered

Literature citations
Contribution of HCN1 variant to sinus bradycardia: A case report.
Yu H.; Gall B.; Newman M.; Hathaway Q.; Brundage K.; Ammer A.; Mathers P.; Siderovski D.; Hull R.W.;
J. Arrhythm. 37:1337-1347(2021)
Cited for: VARIANTS 72-GLY--GLY-74 DEL AND ALA-851; CHARACTERIZATION OF VARIANT ALA-851;

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.