The Mutation Significance Cutoff (MSC) Server

Estimating the impact of genetic variants by gene-specific cutoff significance

Link to the main MSC project webpage

Options 1 and 2 Option 3 Option 4

Option 1: Estimate variants' impact when CADD/PolyPhen-2/SIFT scores not available

Variant input format (in reference genome assembly GRCh37/hg19): "chromosome position ID reference_allele alternative_allele gene_name"

In other words, the first 5 columns of the VCF file (VCF format) and optionally the gene name (if you leave it blank, we will use Ensembl release V75 to estimate the gene name)

Apply MSC to: CADD 1.3 PolyPhen-2 SIFT

Confidence Interval 99% 95% 90%

Database Source HGMD ClinVar

Display database source

Type in your variants columns separated by space, tab or comma.
The maximum length of the text is 4000 characters. If your variants exceed 4000 characters, please use Option 2.

Option 2: As in Option 1 above, via a file provided by user

Variant input format (in reference genome assembly GRCh37/hg19): same as Option 1 above

Example of variant input

Apply MSC to: CADD 1.3 PolyPhen-2 SIFT

Confidence Interval 99% 95% 90%

Database Source HGMD ClinVar

Display database source

Select a file to upload;

Option 3: Estimate Variants' impact with CADD/PolyPhen-2/SIFT scores are provided by the user

Apply MSC to: CADD 1.3 PolyPhen-2 SIFT

Confidence Interval 99% 95% 90%

Database Source HGMD ClinVar

Display database source

Type in each gene_name and score separated with space, tab or comma in the order of the metric selection

Option 4: Estimate the MSC scores for a list of genes

Apply MSC to: CADD 1.3 PolyPhen-2 SIFT

Confidence Interval 99% 95% 90%

Database Source HGMD ClinVar

Display database source

Type in genes separated with space, tab or comma in one or multiple rows

Citation

Itan Y, Shang L, Boisson B, Ciancanelli MJ, Markle J, Martinez-Barricarte D, Scott E, Shah I, Stenson PD, Gleeson D, Cooper DN, Quintana-Murci L, Zhang S-Y, Abel L, and Casanova J-L. The mutation significance cutoff (MSC): gene-level thresholds for variant-level predictions.

In addition, please cite the method on which your MSC calculation was based:
CADD: PMID 24487276; PolyPhen-2: PMID 20354512; SIFT: PMID 19561590

Terms of Usage

The MSC method and server are freely available for all non-commercial users

Contact

In case of problems or questions, please e-mail Yuval Itan at: yitan@rockefeller.edu

The Rockefeller University

St. Giles Laboratory of Human Genetics of Infectious Disease