Table 2.
Population cohort variants and rate of corroborating personal or family history
| Disease | Genea | Number of variants identified | Corroborated history # (%)b |
|---|---|---|---|
| Hereditary breast and ovarian cancer | BRCA1 | 9 | 7 (78%) |
| BRCA2 | 11 | 6 (55%) | |
| Lynch syndrome | MLH1 | 3 | 1 (33%) |
| MSH2 | 1 | 1 (100%) | |
| MSH6 | 3 | 0 (0%) | |
| PMS2 | 2 | 2 (100%) | |
| MYH-associated polyposis | MUTYH | 5 (4 heterozygous, 1 homozygous) | 0 (%) |
| Multiple endocrine neoplasia type 2, familial medullary thyroid cancer | RET | 2 | 1 (50%) |
| Hereditary paraganglioma-pheochromocytoma syndrome | SDHB | 1 | 0 (0%) |
| Hypertrophic cardiomyopathy, dilated cardiomyopathy | MYBPC3 | 9 | 2 (22%) |
| MYH7 | 5 | 1 (20%) | |
| GLA | 2 | 0 (0%) | |
| Arrhythmogenic right ventricular cardiomyopathy | PKP2 | 3 | 0 (0%) |
| Romano-Ward long-QT syndrome types 1, 2, and 3, Brugada syndrome | KCNQ1 | 1 | 0 (0%) |
| KCNH2 | 2 | 0 (0%) | |
| SCN5A | 2 | 1 (50%) | |
| Familial hypercholesterolemia | LDLR | 3 | 2 (67%) |
| APOB | 6 | 5 (85%) | |
| Malignant hyperthermia | RYR1 | 9 | 1 (11%) |
a
Reportable variation in the following genes have not yet been identified in any AGHI population cohort participants to date: TP53, STK11, APC, BMPR1A, SMAD4, VHL, MEN1, PTEN, RB1, SDHD, SDHAF2, SDHC, TSC1, TSC2, WT1, NF2, COL3A1, FBN1, TGFBR1, TGFBR2, SMAD3, ACTA2, MYH11, TNNT2, TNNI3, TPM1, MYL3, ACTC1, PRKAG2, MYL2, LMNA, RYR2, DSP, DSC2, TMEM43, DSG2, PCSK9, ATP7B, OTC, CACNA1S.
b
Corroborated history defined as having a relevant reported personal or family history that was flagged by AGHI criteria.