UniProtKB/Swiss-Prot Q86YC2: Variant p.His46Tyr

Partner and localizer of BRCA2
Gene: PALB2
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Variant information Variant position:

46 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 Histidine (H) to Tyrosine (Y) at position 46 (H46Y, p.His46Tyr). 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 polar (H) to large size and aromatic (Y) 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
Other resources:

Links to websites of interest for the variant.

Variant rs2142457282 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1186 The length of the canonical sequence.
Location on the sequence:

REYSKTLARLQRAQRAEKIK H SIKKTVEEQDCLSQQDLSPQ 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                         REYSKTLARLQRAQRAEKIKHSIKKTVEEQDCLSQQDLSPQ

Mouse                         KEYSRTLARLQRAKRAEKAKNS-KKAIE--DGVPQPEASSQ

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 – 1186	Partner and localizer of BRCA2
Region	1 – 579	DNA-binding (with the preference D loop > dsDNA > ssDNA)
Region	1 – 319	Interaction with BRCA1
Region	1 – 200	Interaction with RAD51
Region	1 – 160	Required for its oligomerization and is important for its focal concentration at DNA damage sites
Mutagenesis	28 – 28	Y -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
Mutagenesis	35 – 35	L -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
Mutagenesis	42 – 42	E -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.

Literature citations
Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer.
Hellebrand H.; Sutter C.; Honisch E.; Gross E.; Wappenschmidt B.; Schem C.; Deissler H.; Ditsch N.; Gress V.; Kiechle M.; Bartram C.R.; Schmutzler R.K.; Niederacher D.; Arnold N.; Meindl A.;
Hum. Mutat. 32:E2176-E2188(2011)
Cited for: VARIANTS TYR-46; GLY-219; CYS-334; SER-337; GLN-414; MET-425; THR-491; ARG-515; ARG-559; GLN-672; VAL-712; LEU-728; SER-864; ALA-917; MET-932; TRP-939; VAL-966; GLU-998; THR-1025; ALA-1043; GLY-1075; ALA-1105; HIS-1114; PRO-1143 AND TYR-1170;

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.