Table 1.
Comparison of clinical characteristics, research variant identified, and CLIA laboratory confirmatory genetic test results
| Clinical characteristics | Research genetic testing and validation | Genetic counseling and/or CLIA Lab confirmatory genetic testing uptake | Survey study | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Documented in EHR prior to research genetic testing | Research result | Clinically validated | ||||||||
| Gender | Dissection age (years) | Family history (1st degree) | Clinical diagnosis (type of dissection and/or genetic condition) | Variant known through clinical testing | Research gene identified | HGVS notation | Research genetic variant validation (MIPs) | Genetic counseling | CLIA lab Variant confirmation (via our study, Invitae) | Enrolled |
| Male | 35–39 | Y | Type A | Y | PRKG1 | p.Arg177Gln | Y | Y | Y | Y |
| Female | 50–54 | Y | Type B | Y | SMAD3 | p.Asn218fs | Y | Y | Y | Y |
| Female | 40–44 | Y | Type A, MFSb | N | FBN1 | p.Arg364* | Y | Y | Y | Y |
| Male | 50–54 | Y | Type B, MFSb | N | FBN1 | p.Arg2057* | Y | Y | Y | Y |
| Female | 40–44 | Y | Type B, MFSb | N | FBN1 | c.1148-2A>G | Y | Y | Y | Y |
| Female | 45–49 | Y | Type A, MFSb | N | FBN1 | p.Glu1811Lys | Y | Y | Y | Y |
| Female | 40–44 | N | Type A, MFSb | N | FBN1 | p.Cys1511Arg | Y | Y | Y | Y |
| Male | 50–54 | Y | Type A | N | FBN1 | p.Asp530Gly | Y | Y | Y | Y |
| Female | 40–44 | Y | Type A, Possible CTD | N | COL3A1 | p.Gly378Aspc | Y | Y | Y | Y |
| Female | 60–64 | N | Type B, MFS | N | FBN1 | c.443-1G>A | Y | Y | Y | Y |
| Male | 30–34 | N | Type A | N | FBN1 | p.Asn2624Ser | Y | Y | N | N |
| Female | 30–34 | Y | Type A, MFSb | Y | FBN1 | p.Asp910Hisc | Y | N | N | N |
| Female | 50–54 | Y | Type B | Y | SMAD3 | p.Asn218fs | Y | N | N | N |
| Male | 20–24 | Y | Type A, MFSb | N | FBN1 | p.Arg2335fsc | Y | N | N | N |
| Male | 20–24 | N | Type A, MFSb | N | FBN1 | p.Cys2496Phe | Y | N | N | N |
| Male | 30–34 | Y | Type A, MFSb | N | FBN1 | p.Gly1316fs | Y | N | N | N |
| Male | 15–19 | Y | Type A, MFSb | N | FBN1 | p.Cys1431Argc | Y | N | N | N |
| Male | 50–54 | Y | Type A | N | SMAD3 | p.Lys116delc | Y | N | N | N |
| Male | 25–29 | N | Aortic rupture and unknown CTD | N | FBN1 | p.Cys2232Tyr | Y | N | N | N |
| Male | 50–54 | Y | Type A | N | LOX | p.Cys244fs | Y | N | N | N |
| Femaled | 45–49 | Y | Type B | N | PRKG1 | p.Arg177Gln | Y | N | N | N |
| Femaled | 15–19 | Y | Type A, MFSb | N | TGFBR2 | p.Trp521* | Y | N | N | N |
| Maled | 25–29 | Y | Type A, MFSb | N | FBN1 | p.Cys2535Trp | Y | N | N | N |
| Maled | 50–54 | Y | Type B, MFSb | N | FBN1 | p.Cys2258Arg | Y | N | N | N |
| Femaled | 30–34 | Y | Type A, MFSb | N | FBN1 | p.Thr564fs | Y | N | N | N |
| Femaled | 20–24 | N | Type A, MFSb | Y | FBN1 | p.Gly1022* | Y | N | N | N |
CLIA Clinical Laboratory Improvement Amendments, CTD connective tissue disease, MFS Marfan Syndrome, MIPs Molecular Inversion Probe Sequencing, N No, Type A Type A aortic dissection, Type B Type B aortic dissection, Y Yes
aHGVS mutation (*) means deletion
bParticipants had a syndromic diagnosis of Marfan Syndrome based on Ghent nosology criteria [28] and the research genetic result aligned with the clinical diagnosis
cGenetic variant not present in gnomAD version 2.1, dbSNP version 151, or ClinVar as of September 30, 2018
dDeceased (n = 5) or lost to follow-up (n = 1)