Who Would Benefit from Broad Spectrum Genetic Testing?

1

A person with a strong family history of hereditary disease

Determine if they carry a gene mutation that increases their risk of developing a condition. If they do have an inherited mutation, they might want to have screening tests to look for disease indications early, or even take steps to try to lower their risk.

2

A person already diagnosed with a hereditary condition

This is especially true if there are other factors to suggest the condition might have been caused by an inherited mutation (such as a strong family history or if the abnormality was diagnosed at a young age). Genetic testing might show if the person has a higher risk of developing a condition considered medically actionable by the American College of Medical Genetics and Genomics. It can also help other family members decide if they want to be tested for the mutation.

3

Family members of a person known to have an inherited gene mutation that increases their risk of a disease

Testing can help them know if they need screening tests to look for disease early, or if they should take steps to try to lower their risk.

Disorder Coverage

• PTEN-related conditions
• Atrial fibrillation
• Biotinidase deficiency
• BRCA1/BRCA2-Associated Hereditary breast and ovarian cancer (HBOC) syndrome
• Brugada syndrome (BrS)
• Carvajal syndrome
• Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
• Constitutional mismatch repair deficiency syndrome (CMMR-D)
• Ehlers-Danlos syndrome (EDS)
• Emery-Dreifuss muscular dystrophy (EDMD)
• Fabry disease
• Familial adenomatous polyposis (FAP), Attenuated familial adenomatous polyposis (AFAP)
• Familial erythrocytosis
• Familial hypercholesterolemia (FH)
• Glycogen storage disease type II (GSDII), also known as Pompe disease

• Hereditary hemochromatosis
• Hereditary hemorrhagic telangiectasia (HHT)
• Hereditary paraganglioma-pheochromocytoma (PGL-PCC) syndrome
• Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis)
• Hirschsprung disease
• Inherited cardiomyopathies
• Inherited retinal dystrophy (IRD)
• Jervell and Lange-Nielsen syndrome (JLNS)
• Juvenile polyposis syndrome (JPS)
• Li Fraumeni syndrome (LFS)
• Loeys-Dietz syndrome (LDS)
• Long QT syndrome (LQTS)
• Lynch syndrome
• Marfan syndrome and other FBN1-related conditions
• MODY
• Multiple endocrine neoplasia type 1 (MEN1)

• Multiple endocrine neoplasia type 2 (MEN2)
• MUTYH-associated polyposis (MAP)
• Myhre syndrome
• Neurofibromatosis type 2
• Ornithine transcarbamylase (OTC) deficiency
• PALB2-related conditions
• Peutz-Jeghers syndrome (PJS)
• Pulmonary arterial hypertension (PAH)
• Retinoblastoma (Rb)
• RYR1-related conditions
• Short QT syndrome (SQTS)
• Smooth muscle dysfunction syndrome
• Thoracic aortic aneurysms and aortic dissections (TAAD)
• Tuberous sclerosis complex
• von Hippel-Lindau syndrome
• Wilson disease
• Wolff-Parkinson-White syndrome (WPW)
• WT1-related disorders

Incidental Findings Panel Best Practices

Preferred Specimen

2mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate Specimens

Saliva
Buccal swab
gDNA

Let's get started!

How to Ship Your Samples

Follow IATA Regulations

Please note that Psomagen sample collection kits are built to protect the samples from being damaged during transport and to comply with the International Air Transport Association (IATA) regulation. If you are using packaging other than that provided by Psomagen, please make sure to follow the "three layers of packaging" rule to avoid the risk of having the package destroyed by the courier:

A primary sample receptacle sealed (collection tube).
A leak-proof specimen bag containing absorbent material.
An outer packaging that meets the local postal regulations and is labeled as “Exempt Human Specimen.”

For more information please refer to page 187 of IATA Dangerous Goods Regulation.

Additional Shipment Requirements

For saliva, ship at room temperature (overnight shipping is not necessary).

For blood, we recommend using overnight shipping the same day that the blood is collected.

Blood can be kept at room temperature for up to 48 hours.
We request that blood is refrigerated no longer than two weeks.
Please do not freeze blood as deletion/duplication analysis is not supported for frozen or partially frozen blood.

Please ship the specimen in a crush-proof container via FedEx Priority Overnight (in accordance with the FedEx Packaging Guidelines for Clinical Samples.

Our US Shipping Address

Attn: Clinical Laboratory Testing Personnel
Psomagen Inc.
1330 Piccard Drive, Ste 103
Rockville, MD 20850

Test for 81 Disorder-related genes

Gene List

ACTA2
ACTC1
ACVRL1
APC
APOB
ATP7B
BAG3
BMPR1A
BRCA1
BRCA2
BTD
CACNA1S
CALM1
CALM2
CALM3
CASQ2
COL3A1

DES
DSC2
DSG2
DSP
ENG
FBN1
FLNC
GAA
GLA
HFE
HNF1A
KCNH2
KCNQ1
LDLR
LMNA
MAX

MEN1
MLH1
MSH2
MSH6
MUTYH
MYBPC3
MYH11
MYH7
MYL2
MYL3
NF2
OTC
PALB2
PCSK9
PKP2
PMS2

PRKAG2
PTEN
RB1
RBM20
RET
RPE65
RYR1
RYR2
SCN5A
SDHAF2
SDHB
SDHC
SDHD
SMAD3
SMAD4
STK11

TGFBR1
TGFBR2
TMEM127
TMEM43
TNNC1
TNNI3
TNNT2
TP53
TPM1
TRDN
TSC1
TSC2
TTN
TTR
VHL
WT1

DNA sequencing involves the extraction of genomic DNA from specimens collected in approved containers and provided the specimen meets required sample minimum quantity (e.g. volume, weight, etc). This is followed by quantification and qualification to ensure the adequacy of amount and purity for sequencing. Subsequently, whole exome sequencing is conducted on an Illumina^TM short read sequencing (SRS) platform (e.g., NovaSeq X Plus^TM) at Psomagen, Inc.’s laboratories (CLIA # 21D2062464, CAP # 8742212).

DNA sequence alignment, variant calling, and variant filtering are performed utilizing the Illumina DRAGEN^TM bioinformatics pipeline (version 4.2.4.) and various tool sets, which align reads to the human reference genome (GRCh38) and identify single nucleotide variants (SNVs) and small insertions/deletions (InDels). Variant annotations are performed using a pipeline available in Fabric Enterprise. Variant review and interpretation are conducted according to the standards and guidelines set forth by the American College of Medical Genetics and Genomics (Richards S, et al., Genet Med., 2015) by Fabric Clinical Labs (CLIA #45D2281059, CAP # 9619501). Only variants classified as pathogenic or likely pathogenic are reported. The following quality filters are applied to all variants: coverage <40x, allele balance outside 0.3-0.7. Variants in the following genes are reported: ACTA2, ACTC1, ACVRL1, APC, APOB, ATP7B, BAG3, BMPR1A, BRCA1, BRCA2, BTD, CACNA1S, CALM1, CALM2, CALM3, CASQ2, COL3A1, DES, DSC2, DSG2, DSP, ENG, FBN1, FLNC, GAA, GLA, HFE, HNF1A, KCNH2, KCNQ1, LDLR, LMNA, MAX, MEN1, MLH1, MSH2, MSH6, MUTYH, MYBPC3, MYH11, MYH7, MYL2, MYL3, NF2, OTC, PALB2, PCSK9, PKP2, PMS2, PRKAG2, PTEN, RB1, RBM20, RET, RPE65, RYR1, RYR2, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SMAD3, SMAD4, STK11, TGFBR1, TGFBR2, TMEM127, TMEM43, TNNC1, TNNI3, TNNT2, TP53, TPM1, TRDN, TSC1, TSC2, TTN, TTR, VHL, WT1.

This test is designed to detect single nucleotide variants (SNVs) and small insertions/deletions (indels). Next-Generation Sequencing (NGS) coverage may vary across the genome, potentially resulting in missed variants in regions with low coverage depth. Some genetic abnormalities may be undetectable with the current version of this test. While the DRAGEN bioinformatics pipeline demonstrates high accuracy for variant calling, there remains a possibility of false positive or false negative results due to variant interpretation which relies on current scientific knowledge and available databases. This may lead to the reclassification of reported variants as new information emerges from ongoing research and is updated in the ACMG guidelines. Furthermore, systematic chemical, computational, or human errors may contribute to false positives or false negatives of DNA variants. For any reported variants, confirmation by orthogonal technology and subsequent consultation with a genetic counselor or qualified healthcare provider can help to establish definitive risk. This result should be considered preliminary until such confirmation has been performed.

Clinical management for this individual should be based on personal and family history, along with other relevant information. If considered relevant to this individual’s clinical presentation and/or family history, targeted testing of appropriate family members of this individual for the reported variants may help to interpret these results. For assistance with the interpretation of these results, healthcare professionals may contact Psomagen directly at (301) 251-1007 or support@psomagen.com.

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CLINICAL CAPABILITIES // Genetic testing

ACMG Incidental Findings