Table 3 Variants identified in Geisinger MyCode participants between June 2016 and October 2019 (n=80)
Condition | Gene | Variant (transcript:cDNA (protein)) | ClinVar variant ID | Reported genotype/phenotype relationship | Participants identified via MyCode (n=65) | Participants previously aware of molecular or clinical diagnosis (n=15) |
|---|---|---|---|---|---|---|
Multiple endocrine neoplasia type 1 | MEN1 | NM_130804.2:c.1267G>A (p.Asp423Asn) | 16703 | N/A | 2 | 0 |
MEN1 | NM_130804.2:c.249_252del (p.Ile85SerfsTer33) | 16693 | N/A | 0 | 2 | |
MEN1 | NM_130804.2:c.307del (p.Leu103CysfsTer16) | 200996 | N/A | 0 | 2 | |
Multiple endocrine neoplasia type 2 | RET | NM_020975.4:c.2671T>G (p.Ser891Ala) | 13951 | Moderate MTC risk, ~10% incidence of pheochromocytoma and hyperparathyroidism | 26 | 6 |
RET | NM_020975.4:c.2410G>A (p.Val804Met) | 37102 | 4 | 1 | ||
RET | NM_020975.4:c.1998G>T (p.Lys666Asn) | 24932 | Other variants impacting this codon classified as moderate MTC risk, ~10% incidence of pheochromocytoma and hyperparathyroidism | 1 | 0 | |
RET | NM_020975.4:c.1859G>A (p.Cys620Tyr) | 13916 | Other variant(s) impacting this codon classified as moderate, ~10–30% incidence of pheochromocytoma, and ~10% incidence of pheochromocytoma and hyperparathyroidism | 0 | 1 | |
RET | NM_020975.4:c.1858T>G (p.Cys620Gly) | 24905 | 0 | 1 | ||
Hereditary paraganglioma and pheochromocytoma syndrome | SDHAF2 | NM_017841.2:c.37-1G>C | 806678 | Parent of origin effect | 1 | 0 |
SDHAF2 | NM_017841.2:c.305_306insA (p.Asn103GlufsTer4) | 532508 | 1 | 0 | ||
SDHB | NM_003000.2:c.343C>T (p.Arg115Ter) | 197210 | N/A | 2 | 1 | |
SDHB | NM_003000.2:c.137G>A (p.Arg46Gln) | 183793 | N/A | 2 | 0 | |
SDHB | NM_003000.2:c.286+2T>A | 140773 | N/A | 2 | 0 | |
SDHB | NM_003000.2:c.380T>G (p.Ile127Ser) | 183814 | N/A | 2 | 0 | |
SDHB | NM_003000.2:c.72+1G>T | 142764 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.445_446insTATGG (p.Gln149LeufsTer11) | 504902 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.491delA (p.Gln164ArgfsTer11) | 528750 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.600G>T (p.Trp200Cys) | 183747 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.688C>T (p.Arg230Cys) | 185077 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.689G>T (p.Arg230Leu) | 184933 | N/A | 1 | 0 | |
SDHB | NM_003000.2:c.725G>A (p.Arg242His) | 12781 | N/A | 1 | 0 | |
SDHC | NM_003001.3:c.397C>T (p.Arg133Ter) | 183753 | N/A | 5 | 0 | |
SDHC | NM_003001.3:c.43C>T (p.Arg15Ter) | 41776 | N/A | 4 | 0 | |
SDHD | NM_003002.3:c.242C>T (p.Pro81Leu) | 6896 | Parent of origin effect | 3 | 0 | |
SDHD | NM_003002.3:c.112C>T (p.Arg38Ter) | 6893 | 1 | 0 | ||
SDHD | NM_003002.3:c.53-1_53delGCinsTT | 579812 | 1 | 0 | ||
Von Hippel-Lindau syndrome | VHL | NM_000551.3:c.562C>G (p.Leu181Val) | 2225 | VHL type 2C | 1 | 0 |
VHL | NM_000551.3:c.292T>C (p.Tyr98His) | 2223 | VHL Type 2A | 0 | 1 |