UniProtKB/Swiss-Prot P15918: Variant p.Arg474Cys

V(D)J recombination-activating protein 1
Gene: RAG1
Feedback?

Variant information Variant position:

474 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 Arginine (R) to Cysteine (C) at position 474 (R474C, p.Arg474Cys). 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 basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 relatively late onset of infections and isolated T-cell lymphopenia; likely pathogenic; also found in a patient with T and B cell immunodeficiency and progressive multifocal leukoencephalopathy; decreases recombination activity; no effect on protein abundance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs199474678 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1043 The length of the canonical sequence.
Location on the sequence:

LEAIMQGKGSGLQPAVCLAI R VNTFLSCSQYHKMYRTVKAI 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                         LEAIMQGKGSGLQPAVCLAIRVNTFLSCSQYHKMYRTVKAI

Mouse                         LEAIMQGRGSGLQPAVCLAIRVNTFLSCSQYHKMYRTVKAI

Pig                           LEAIMRGQGSGLQPAVCLAIRVNTFLSCSQYHKMYRTVKAI

Rabbit                        LEAIMQGRGSGLQPAVCLAIRVNTFLSCSQYHKMYRTVKAI

Chicken                       LEAIMQGRGSGLHPAVCLAIRINTFLSCSQYHKMYRTVKAV

Xenopus laevis                LEAIMEGRGAGLHPAVCLAIRVNTFLSCSQYHKMYRTVKAT

Zebrafish                     LEAMMQGRGFGLHPAVCLAIRVNTFLSCSQYHKMYRTVKAT

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 – 1043	V(D)J recombination-activating protein 1

Literature citations
Highly variable clinical phenotypes of hypomorphic RAG1 mutations.
Avila E.M.; Uzel G.; Hsu A.; Milner J.D.; Turner M.L.; Pittaluga S.; Freeman A.F.; Holland S.M.;
Pediatrics 126:E1248-E1252(2010)
Cited for: VARIANT CYS-474; Evaluation of RAG1 mutations in an adult with combined immunodeficiency and progressive multifocal leukoencephalopathy.
Schroeder C.; Baerlecken N.T.; Pannicke U.; Doerk T.; Witte T.; Jacobs R.; Stoll M.; Schwarz K.; Grimbacher B.; Schmidt R.E.; Atschekzei F.;
Clin. Immunol. 179:1-7(2017)
Cited for: VARIANTS ASP-375 AND CYS-474; CHARACTERIZATION OF VARIANT CYS-474;

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.