Sequence variations are described basically as recommended by the Ad-Hoc Nomenclature Committee of the Human Genome Variation Society (HGVS). For the most recent recommendations see the HGVS "Nomenclature for the description of sequence variants" web page. The most recent publication on the subject is by den Dunnen JT & Antonarakis SE (2000), Hum.Mut. 15: 7-12.
NOTE: in all cases, unless indicated otherwise, all data of an entry are as reported by the author(s)/submitter.
Path.: Variant pathogenicity, in the format Reported/Concluded; '+' indicating the variant is pathogenic, '+?' probably pathogenic, '-' no known pathogenicity, '-?' probably no pathogenicity, '?' effect unknown.
Exon: Exon numbering.
DNA change: Variation at DNA level.
BIC DNA change: Variation at DNA-level.
Protein change: Predicted effect of change on protein (usually without experimental proof!)
- ? = unknown
- (0) = change expected to abolish translation
- ?fs = frame shift, but observed phenotype does not fit with prediction (for instance less severe phenotype (BMD) observed, more severe phenotype (DMD) expected)
- ?no fs = frame shift, but observed phenotype does not fit with prediction (for instance more severe phenotype (DMD) observed, less severe phenotype (BMD) expected)
- del = causes deletion
- fs = causes frame shift
- fs? = effect on reading frame very likely (no experimental proof)
- (fs?) = might affect the reading frame (no experimental proof)
- no fs = does not cause frame shift
- X = stop codon (nonsense)
IARC Class:
| Class | Description | Probability of being pathogenic |
| 5 | Definitely pathogenic | >0.99 |
| 4 | Likely pathogenic | 0.95-0.99 |
| 3 | Uncertain | 0.05-0.949 |
| 2 | Likely not pathogenic or of little clinical significance | 0.001-0.049 |
| 1 | Not pathogenic or of no clinical significance | <0.001 |
- 5 - Definitely pathogenic
- 4 - Likely pathogenic
- 3 - Uncertain
- 2 - Likely not pathogenic or of little clinical significance
- 1 - Not pathogenic or of no clinical significance
Key Observational Reference: Primary reference
- Goldgar et al., AJHG 75: 535-544, 2004.
- Tavtigian et al., Human Mutation 29: 1342-1354, 2008.
- Wu, K. et al., Cancer Research 65: 417-426, 2005.
- Tavtigian, S.V. et al., Journal of Medical Genetics 43: 295-305, 2006.
- Chenevix-Trench, G. et al., Cancer Research 66: 2019-2027, 2006.
- Spurdle AB et al., J Clin Oncol, 26: 1657-1663, 2008.
- Easton DF et al., Am J Hum Genet, 81: 873-883, 2007.
- Farrugia DJ et al., Cancer Research 68:3523-3531, 2008.
- Spearman AD et al., J Clin Oncol, 26:5393-5400, 2008.
- Walker LC et al., Human Mutation 31: E1484-E1505, 2010
- Whiley et al., Human Mutation 32: 678-687, 2011
- Domchek SM et al., Cancer Discov 3: 399-405 (2013).
- Thomassen M et al., Breast Cancer Res Treat. 2012 Apr;132(3):1009-23.
- Whiley PJ et al., PLoS One. 2014 Jan 28;9(1):e86836.
Prior P reference: Secondary reference
- Goldgar et al., AJHG 75: 535-544, 2004.
- Tavtigian et al., Human Mutation 29: 1342-1354, 2008.
- Wu, K. et al., Cancer Research 65: 417-426, 2005.
- Tavtigian, S.V. et al., Journal of Medical Genetics 43: 295-305, 2006.
- Chenevix-Trench, G. et al., Cancer Research 66: 2019-2027, 2006.
- Easton DF et al., Am J Hum Genet, 81: 873-883, 2007.
- Vallée et al., manuscript submitted, 2015
Splicing prior P: Splicing prior probability
Other Prior P: Custom Priors other than missense or splice (full legend)
Combined prior P: Combined prior probability
Co-occurrence LR: Co-occurrence likelihood ratio
case-control LR: case-control likelihood ratios from the Illumina Collaborative Oncological Gene-environment Study array (full legend)
Comments: to include additional refs/provenance and other warnings/additional relevant information
Disease: Disease phenotype of the patient(s).
Reference: Literature reference with possible link to publication in PubMed, dbSNP entry or other online resource. "Submitted:" indicates that the mutation was submitted directly to this database by the laboratory indicated.
Template: Variant detected in DNA, RNA and/or Protein.
- DNA
- RNA
- Protein
Technique: Technique used to reveal the change reported. For all methods, confirmation by sequencing (SEQ) is included. Select SEQ only when none of other techniques was used.
- BESS = Base Excision Sequence Scanning
- CMC = Chemical Mismatch Cleavage
- DGGE = Denaturing-Gradient Gel-Electrophoresis
- DHPLC = Denaturing High-Performance Liquid Chromatography
- DOVAM = Detection Of Virtually All Mutations (SSCA variant)
- DSCA = Double-Strand DNA Conformation Analysis
- HD = HeteroDuplex analysis
- IHC = Immuno-Histo-Chemistry
- mPCR = multiplex PCR
- MAPH = Multiplex Amplifiable Probe Hybridisation
- MLPA = Multiplex Ligation-dependent Probe Amplification
- PAGE = Poly-Acrylamide Gel-Electrophoresis
- PCR = Polymerase Chain Reaction
- PTT = Protein Truncation Test
- RT-PCR = Reverse Transcription and PCR
- SEQ = SEQuencing
- Southern = Southern Blotting
- SSCA = Single-Strand DNA Conformation Analysis (SSCP)
- Western = Western Blotting
# Reported: Number of times this case has been reported