UniProtKB/SwissProt variant VAR

Variant information

Variant position:

71

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

Type of variant:

Unclassified

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Lysine (K) at position 71 (R71K, p.Arg71Lys).

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:

Similar physico-chemical property. Both residues are large size and basic.

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

Involvement in disease:

Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:10323242, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:12427738, ECO:0000269|PubMed:12442275, ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:18285836, ECO:0000269|PubMed:21473589, ECO:0000269|PubMed:23867111, ECO:0000269|PubMed:28364669, ECO:0000269|PubMed:7545954, ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493, ECO:0000269|PubMed:7939630, ECO:0000269|PubMed:8554067, ECO:0000269|PubMed:8723683, ECO:0000269|PubMed:8776600, ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9609997, ECO:0000269|PubMed:9760198}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In BC; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80356913 [ dbSNP | Ensembl ]

Sequence information

Variant position:

71

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:

LLNQKKGPSQCPLCKNDITK R SLQESTRFSQLVEELLKIIC

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                         LLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIC

Gorilla                       LLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIC

                              LLNQRKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIH

Rhesus macaque                LLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIH

Chimpanzee                    LLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIC

Mouse                         LLNQKKGPSQCPLCKNEITKRSLQGSTRFSQLAEELLRIMA

Rat                           LLNQKKGPSQCPLCKNEITKRSLQGSARFSQLVEELLKIID

Bovine                        LLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIH

Caenorhabditis elegans        CFERKR-KVQCPICRSVLDKRSCRDTYQITMAVQNYLKLSE

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
Alternative sequence	64 – 1863	Missing. In isoform 2.
Mutagenesis	71 – 71	R -> G. No effect on interaction with BAP1.
Turn	70 – 72

Literature citations

Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany.
Meyer P.; Voigtlaender T.; Bartram C.R.; Klaes R.;
Hum. Mutat. 22:259-259(2003)
Cited for: VARIANTS BC GLY-61; LYS-71; GLN-866; TYR-888; ILE-1139; GLY-1210 AND PRO-1297; VARIANTS BROVCA1 TYR-835 AND PRO-1786;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Arg71Lys