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GENEID • ADVANCED MOLECULAR DIAGNOSTICS, LLC .
Seshamma T. Reddy M.D., Ph.D. •Medical Director
Daniel Cohen M.D. •Scientific Director
19 Spear Road • Suite 312 • Ramsey, NJ • 07446
P • 866.436.3263 F • 201.962.7393
GeneIDLab.com • [email protected]
Date • 03.06.2014
NEXT GENERATION SEQUENCING- PREVENTEST ®-MOLECULAR REPORT
PATIENT
Patient Name: XXX
AMD access#: GEN-14-XX
Date of Birth: XX/XX/XXX
Gender: F
SPECIMEN INFORMATION
Specimen : Buccal swab.
Date Received: 0X/X/20XX
Initiation of Testing: 0X/XX/20XX
Completion of Testing: 0X/0X/20XX
ORDERED BY
Ordering Physician’s: Dr xxxx
PREVENTEST-MOLECULAR PANEL*
* PREVENTEST® MOLECULAR PANEL is a full risk sequencing of germline mutations involved in familial cancer predisposition. The panel
described as complementary information, interrogates 34 germline key-cancer predisposition genes, targeting mutational hotspots associated
with both common and rare familial cancer syndromes. All translated exons and immediately adjacent intronic regions are sequenced. Single
nucleotides polymorphisms, duplications, insertions, deletions, and variants of uncertain significance can be detected.
METHODOLOGY
TARGET GENE(S): 34 germline cancer genes predisposition
A molecular library was prepared from 40 ng of genomic DNA isolated from buccal swab sample received in our lab by the name of “XXXXX ”.
After quantification, a pool of 10,400 primer pairs were used to amplify the coding exons of target genes. A template-positive ion sphere
particles for up to 200 base-read sequencing was constructed and loaded into a microchip for sequencing. The DNA reading was performed by
next generation- Ion Semiconductor Sequencing, based on the detection of hydrogen ions that are released during the polymerization of DNA.
Genetic data was analyzed by bioinformatics software developed by Life Technologies, Inc, and stored under Variant call format (VCF). (1)(2)
(1)Bio-IT World, Davies, K. Powering Preventative Medicine. Bio-IT World 2011.
(2)GenomeWeb DNA Electronics Licenses IP to Ion Torrent. August 2010.
RESULT- SUMMARY
MUTYH : DELETERIOUS MUTATION DETECTED (D.V.D.)
GENE
MUTYH
RESULT
POSITIVE
DESCRIPTION
DVD
Legend:
DVD: Deleterious variant detected, associated with a significantly increased cancer risk.
SVD: Suspected variant detected. Evidence indicates with a high degree of certainty that the variant is associated with significantly increased
cancer risk.
VUS: Variant of Uncertain Significance. There is insufficient evidence to determine if the variant is associated with an increased cancer risk.
PR: Polymorphism reported. Evidence indicates with a high degree of certainty that the variant is not associated with an increased cancer risk.
BP: Benign polymorphism. The change is not associated with an increased cancer risk. Because these variants are clinically benign, they are not
reported.
Advanced Molecular Diagnostics, LLC • 19 Spear Road Suite 312 • Ramsey, NJ 07446 • P 201.825.0186 • F 201.962.7393 •
[email protected] CLIA # 31D2053667 • NPI # 179002354
GeneIDLab.com •
P: 2 OF 4
GENEID • ADVANCED MOLECULAR DIAGNOSTICS, LLC .
Seshamma T. Reddy M.D., Ph.D. •Medical Director
Daniel Cohen M.D. •Scientific Director
19 Spear Road • Suite 312 • Ramsey, NJ • 07446
P • 866.436.3263 F • 201.962.7393
GeneIDLab.com • [email protected]
Date • 03.06.2014
NEXT GENERATION SEQUENCING- PREVENTEST ®-MOLECULAR REPORT
Patient Name: XXXXXXXX
AMD access#: GEN14-XXXX
Ordering Physician’s: Dr XXXXXXXXXX
*Disclaimer
Some genes displayed as "Complementary Information" have not been yet validated for clinical use. The contents of this information is for
research use only and not intent for any human therapeutic or diagnostic use.”
MUTYH: POSITIVE FOR A DELETERIOUS MUTATION
GENE
APC
ATM
BARD-1
BMPR1A
BRAF
BRCA-1
BRCA-2
BRIP-1
CDH-1
CDK-4
CDKN-2A
CHEK-2
EGFR
ELAC-2
EPCAM
HRAS-1
KRAS
RESULT
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
DESCRIPTION
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
GENE
MLH-1
MRE-11A
MSH-2
MSH-6
MUTYH
NBN
PALB-2
PMS-2
PTCH-1
PTEN
RAD-50
RAD-51C
RAD-51D
RET
SMAD-4
STK-11
TP-53
RESULT
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
POSITIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
DESCRIPTION
BP
BP
BP
BP
DVD
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
BP
Legend:
DVD: Deleterious variant detected, associated with a significantly increased cancer risk.
SVD: Suspected variant detected. Evidence indicates with a high degree of certainty that the variant is associated with significantly increased
cancer risk.
VUS: Variant of Uncertain Significance. There is insufficient evidence to determine if the variant is associated with an increased cancer risk.
PR: Polymorphism reported. Evidence indicates with a high degree of certainty that the variant is not associated with an increased cancer risk.
BP: Benign polymorphism. The change is not associated with an increased cancer risk. Because these variants are clinically benign, they are not
reported.
MUTYH- D.V.D. DESCRIPTION
FINDING
MUTYH missense, exon 13
CODON
c.1187G>A
PROTEIN
p.Gly396Asp/bi-allelic
INTERPRETATION
Deleterious
Advanced Molecular Diagnostics, LLC • 19 Spear Road Suite 312 • Ramsey, NJ 07446 • P 201.825.0186 • F 201.962.7393 • GeneSiteLab.com •
[email protected] CLIA # 31D2053667 • NPI # 17900235
P: 3 OF 4
GENEID • ADVANCED MOLECULAR DIAGNOSTICS, LLC .
Seshamma T. Reddy M.D., Ph.D. •Medical Director
Daniel Cohen M.D. •Scientific Director
19 Spear Road • Suite 312 • Ramsey, NJ • 07446
P • 866.436.3263 F • 201.962.7393
GeneIDLab.com • [email protected]
Date • 03.06.2014
NEXT GENERATION SEQUENCING- PREVENTEST ®-MOLECULAR REPORT
Patient Name: XXXXXXXX
AMD access#: GEN14-XXXX
Ordering Physician’s: Dr XXXXXXXXXX
COMMENTS & CONCLUSION
The results of this analysis is consistent with a MUTYH single nucleotide polymorphisms (SNP) or missense mutation at exon 13 of the MUTYH
gene noted as c.1187G>A (rs36053993) which results in an amino acid change from glycine to aspartic acid in the MUTYH protein position 396
noted as p.Gly396Asp or G396D. This mutation was found as bi-allelic. Prediction algorithms indicate this finding as “disease causing” (1-3).
Studies in high-risk families indicate an association between germline MUTYH-G396D and Colorectal Adenomatous Polyposis (Autosomal
Recessive; Multiple Colorectal Adenomas, Autosomal Recessive and/or MYH-Associated Polyposis).
MUTYH-associated polyposis (MAP), caused by biallelic mutations in MUTYH, is characterized by a greatly increased lifetime risk of colorectal
cancer (CRC) (43% to almost 100% in the absence of timely surveillance).(GeneReviews, Randall Brand, MD, Maartje Nielsen, MD, Henry
Lynch, MD, and Elena Infante, MS, CGC. October 4, 2012.)
Sequencing on thirty three other genes, included in the panel descripted above, showed variants consistent with intron and synonymous
polymorphisms and are considered benign (1-6).
1. Flicek et al. Nucleic Acids Research 2013 41 Database issue:D48-D55
doi: 10.1093/nar/gks1236
2. Helga Thorvaldsdóttir, James T. Robinson, Jill P. Mesirov. Integrative Genomics Viewer (IGV): high-performance genomics data visualization
and exploration. Briefings in Bioinformatics 2012.
3. Genome Res. 2009 Jul;19(7):1316-23. doi: 10.1101/gr.080531.108. Epub 2009 Jun 4.
4. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res.
2001 Jan 1;29(1):308-11.
5. Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011). LOVD v.2.0: the next generation in gene variant databases.
Hum Mutat. 2011 May;32(5):557-63.
6. Stenson et al. 2013 The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics,
diagnostic testing and personalized genomic medicine. Hum Genet in press.
GIVEN THE RESULTS WE RECOMMEND:
Surveillance: Individuals with biallelic MUTYH germline mutations:
•In the US: pan-colonoscopy every one to two years beginning at age 25-30 years; following colectomy, endoscopy of any remaining colon or
rectum every one to two years. Upper endoscopy and side viewing duodenoscopy every 3-5 years beginning at age 30-35 years. For
extraintestinal malignancies surveillance is for existing protocols offered to the general population.
•In Europe: pan-colonoscopy beginning at age 18-20 years; upper endoscopy with side viewing duodenoscopy beginning at age 25-30 years;
follow up depending on disease severity.
•Individuals with a heterozygous MUTYH germline mutation: offer average moderate-risk colorectal screening based on family history.
Evaluation of relatives at risk: Offer molecular genetic testing for the familial mutations to all sibs of an individual with genetically confirmed
MAP in order to reduce morbidity and mortality through early diagnosis and treatment.
Advanced Molecular Diagnostics, LLC • 19 Spear Road Suite 312 • Ramsey, NJ 07446 • P 201.825.0186 • F 201.962.7393 • GeneIDLab.com • [email protected]
CLIA # 31D2053667 • NPI # 17900235
P: 4 OF 4
GENEID • ADVANCED MOLECULAR DIAGNOSTICS, LLC .
Seshamma T. Reddy M.D., Ph.D. •Medical Director
Daniel Cohen M.D. •Scientific Director
19 Spear Road • Suite 312 • Ramsey, NJ • 07446
P • 866.436.3263 F • 201.962.7393
GeneIDLab.com • [email protected]
Date • 03.06.2014
NEXT GENERATION SEQUENCING- PREVENTEST ®-MOLECULAR REPORT
Patient Name: XXXXXXXX
AMD access#: GEN14-XXXX
Ordering Physician’s: Dr XXXXXXXXXX
Genetic counseling. MAP is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of
being affected, a 50% chance of being a carrier with a small increased risk for CRC, and a 25% chance of being unaffected and not a carrier.
It is recommended that these test results be communicated to the patient in a setting that includes appropriate genetic counseling by a
licensed/certified genetic counselor.
These test results should only be used in conjunction with the patient’s clinical history and any previous analysis of appropriate family
members. Further clinical assessment and family history is recommended to determine patient risk for hereditary cancer.
Advanced Molecular Diagnostics, LLC • 19 Spear Road Suite 312 • Ramsey, NJ 07446 • P 201.825.0186 • F 201.962.7393 • GeneIDLab.com • [email protected]
CLIA # 31D2053667 • NPI # 17900235