UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1775

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

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:

From Methionine (M) to Lysine (K) at position 1775 (M1775K, p.Met1775Lys).

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 (M) to large size and basic (K)

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:

In BC; strongly reduced transcription transactivation; abolishes interaction with BRIP1 and RBBP8.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs41293463 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1775

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

1863

The length of the canonical sequence.

Location on the sequence:

SQDRKIFRGLEICCYGPFTN M PTDQLEWMVQLCGASVVKEL

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                         SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKEL

Gorilla                       SQDRKIFRGLDICCYGPFTNMPTDQLEWMVQL---CGASVV

                              SQDRKIFRGLEICCYGPFTNMPTDQLEWMVHL---CGASVV

Rhesus macaque                SPDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Chimpanzee                    SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Mouse                         SRE-KLFKGLQVYCCEPFTNMPKDELERMLQL---CGASVV

Rat                           SQE-KLFEGLQIYCCEPFTNMPKDELERMLQL---CGASVV

Bovine                        SRDKKIFKGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Caenorhabditis elegans        DEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEIL

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 – 1863	Breast cancer type 1 susceptibility protein
Domain	1756 – 1855	BRCT 2
Alternative sequence	64 – 1863	Missing. In isoform 2.
Mutagenesis	1755 – 1755	S -> A. No effect on in vitro phosphorylation by ATR.
Beta strand	1773 – 1775

Literature citations

Pathogenicity of the BRCA1 missense variant M1775K is determined by the disruption of the BRCT phosphopeptide-binding pocket: a multi-modal approach.
Tischkowitz M.; Hamel N.; Carvalho M.A.; Birrane G.; Soni A.; van Beers E.H.; Joosse S.A.; Wong N.; Novak D.; Quenneville L.A.; Grist S.A.; Nederlof P.M.; Goldgar D.E.; Tavtigian S.V.; Monteiro A.N.; Ladias J.A.; Foulkes W.D.;
Eur. J. Hum. Genet. 16:820-832(2008)
Cited for: X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 1649-1859 OF VARIANT BC LYS-1775; VARIANT BC LYS-1775; CHARACTERIZATION OF VARIANT BC LYS-1775;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Met1775Lys