UniProtKB/Swiss-Prot Q86YC2: Variant p.Leu939Trp

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

939 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 Leucine (L) to Tryptophan (W) at position 939 (L939W, p.Leu939Trp). 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 (L) to large size and aromatic (W) 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
Variant description:

May be associated with breast cancer susceptibility; reduces interaction with BRCA2, RAD51 and XRCC3; decreases double-stranded DNA break-initiated homologous recombination; increases sensitivity to IR. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs45478192 [ dbSNP | Ensembl ]

Sequence information Variant position:

939 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:

VLQIVPVPDVYNLVCVALGN L EIREIRALFCSSDDESEKQV 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                         VLQIVPVPDVYNLVCVALGNLEIREIRALFCSSDDESEKQV

Mouse                         VLQIVPVPDVYNLICVALGSLEIREIRALLCSSGDDSEKQV

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
Repeat	917 – 961	WD 2
Region	775 – 1186	Required for interaction with POLH and POLH DNA synthesis stimulation
Region	853 – 1186	Interaction with RAD51, BRCA2 and POLH
Beta strand	938 – 947

Literature citations
Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.
Park J.Y.; Singh T.R.; Nassar N.; Zhang F.; Freund M.; Hanenberg H.; Meetei A.R.; Andreassen P.R.;
Oncogene 33:4803-4812(2014)
Cited for: FUNCTION; INTERACTION WITH BRCA2; RAD51C; RAD51 AND XRCC3; MUTAGENESIS OF THR-1030; CHARACTERIZATION OF VARIANTS TRP-939 AND PRO-1143; 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.