1.Vierimaa, O. Etal. Pituitary Adenoma Predisposition Caused by Germline Mutations in The
Mutation or variant (corresponding protein change) / Adenoma subtype (n) / Size (n) / Sex (n) / Age at diagnosis (years) (n) / Study
Nonsense
c.40C˃T
(Gln14*)‡ / GH-secreting (3), prolactinoma, GH-secreting+prolactinoma / N/A (5) / M (2), F (2), N/A / 35 (2), 36, 41, N/A / Vierimaa, O. etal.1, Georgitsi, M. etal.2, Raitila, A. etal.3
c.58G˃T
(Glu20*) / GH-secreting / MA / M / 14 / Cuny, T. etal.4
c.64C˃T
(Arg22*) / GH-secreting (2) / MA (2) / M (2) / 10, 24 / Barlier, A. etal.5, Tichomorowa, M.A. etal.6
c.55C˃T
(Gln184*) / GH-secreting / N/A / M / 21 / Tichomorowa, M.A. etal.6
c.601A˃T
(Lys201*) / GH-secreting (2) / MA (2) / M, F / 24, 27 / Cazabat, L. etal.7
c.721A˃T
(Lys241*) / Prolactinoma / GA / M / 18 / Stratakis, C.A. etal.8
c.783C˃G
(Tyr261*) / GH-secreting (2) / MA, GA / M (2) / 17, 28 / Tichomorowa, M.A. etal.6, Cazabat, L. etal.9
c.910C˃T
(Arg304*)‡ / GH-secreting (3) / GA (2), N/A / M (2), F / 17 (2), 25 / Tichomorowa, M.A. etal.6, Cazabat, L.etal.9
Frameshift
c.88–89delGA
(Asp30Trpfs*14) / NFPA / MA / M / 39 / Tichomorowa, M.A. etal.6
c.245–249delAAGGG
(Glu82Glyfs*8) / GH-secreting / GA / M / 15 / Tichomorowa, M.A. etal.6
c.350del
(Gly117Alafs*39) / GH-secreting (3), prolactinoma (3) / MA (4), G, N/A / M (5), F / 13, 16, 18, 20 (2), 30 / Cuny, T. etal.4, Tichomorowa, M.A. etal.6, Cazabat, L. etal.9
c.339–340insACCC
(Pro114Thrfs*17) / GH-secreting / MA / F / 14 / Stratakis, C.A. etal.8
c.404delA
(His135Leufs*21) / GH-secreting / MA / M / 14 / Cazabat, L. etal.7
c.630delG
(Asn211Thrfs*4) / NFPA / MA / M / 15 / Cuny, T. etal.4
c.752delT
(Leu251Argfs*52) / ACTH-secreting / MA / F / 25 / Cazabat, L. etal.9
c.824dupA
(His275Glnfs*13) / GH-secreting / N/A / M / 8 / Georgitsi, M. etal.2
Duplication
c.805–825dup
(Phe269–His275dup)‡ / GH-secreting+prolactinoma / MA / M / 14 / Cazabat, L. etal.9
Deletion
c.66–71delAGGAGA
(Gly23–Glu24del) / GH-secreting / N/A / M / 20 / Georgitsi, M. etal.2
c.736–738delGAG
(Glu246del) / NFPA / MA / M / 20 / Cuny, T. etal.4
c.742–744delTAC
(Tyr248del) / GH-secreting / MA / M / 19 / Georgitsi, M. etal.10
Initiation codon
c.2T˃C
(effect unknown) / GH-secreting / MA / M / 8 / Personnier, C. etal.11
Missense
c.26G˃A
(Arg9Gln) / GH-secreting, prolactinoma, ACTH-secreting / MA (2), MI / F (3) / 14, 21, 39 / Cazabat, L. etal.9, Oriola, J. etal.12
c.90T˃G
(Asp30Glu) / GH-secreting / MA / M / 23 / Cai, F. etal.13
c.166C˃T
(Arg56Cys) / Prolactinoma / GA / M / 26 / Tichomorowa, M.A. etal.6
c.145G˃A
(Val49Met) / GH-secreting / MA / M / 28 / Iwata, T. etal.14
c.174G˃C
(Lys58Asn) / Prolactinoma, gonadotroph / MA, GA / M, F / 20, 32 / Tichomorowa, M.A. etal.6, Cazabat, L. etal.9
c.250G˃A
(Glu84Lys) / GH-secreting / MA / F / 20 / Tichomorowa, M.A. etal.6
c.308A˃G
(Lys103Arg) / ACTH-secreting / MI / M / 6 / Stratakis, C.A. etal.8
c.509T˃C
(Met170Thr) / GH-secreting / MA / M / 32 / Cazabat, L. etal.9
c.563G˃A
(Arg188Gln) / Prolactinoma / MI / F / 24 / Cazabat, L. etal.9
c.584T˃C
(Val195Ala) / Prolactinoma / GA / M / 12 / Tichomorowa, M.A. etal.6
c.784G˃A
(Asp262Asn) / GH-secreting / MA / M / 35 / Cai, F. etal.13
c.803A˃G
(Tyr268Cys) / Prolactinoma / GA / M / 28 / Tichomorowa, M.A. etal.6
c.811C˃T
(Arg271Trp)‡ / GH-secreting / GA / M / 18 / Tichomorowa, M.A. etal.6
c.829G˃C
(Ala277Pro) / GH-secreting / MA / M / 12 / Tichomorowa, M.A. etal.6
c.871G˃A
(Val291Met) / GH-secreting / N/A / F / 30 / Occhi, G. etal.15
c.872T˃A
(Val291Glu) / GH-secreting + prolactinoma / MA / M / 21 / Cazabat, L. etal.9
c.881T˃C
(Leu294Pro) / GH-secreting / MA / F / 10 / Cuny, T. etal.4
c.911G˃A
(Arg304Gln)‡ / GH-secreting (2), prolactinoma (4), ACTH-secreting / MI (3), M (3), N/A / M (3), F 93), N/A / 15, 25, 26, 27, 36, 38, 67 / Georgitsi, M. etal.2, Cuny, T. etal.4, Tichomorowa, M.A. etal.6, Cazabat, L. etal.9, Occhi, G. etal.15
c.955G˃A
(Glu319Lys) / GH-secreting / MA / M / 11 / Cai, F. etal.13
c.976G˃A
(Gly326Arg) / GH-secreting / GA / M / 30 / Cai, F. etal.13
Intronic
c.469–2A˃G
(?) / GH-secreting+prolactinoma, prolactinoma / MA (2) / M (2) / 16, 40 / Cazabat, L. etal.9
c.468+1G˃A
(?) / GH-secreting / MI / F / 62 / Occhi, G. etal.15
c.280-1G˃C
(?) / GH-secreting / N/A / M / 20 / Georgitsi, M. etal.2
c.787+24C˃T
(?) / GH-secreting / MA / F / 44 / Oriola, J. etal.12
Synonymous
c.591G˃A
(=) / GH-secreting / MA / F / 23 / Tichomorowa, M.A. etal.6
c.687G˃A
(=) / GH-secreting / MA / M / 24 / Cai, F. etal.13
c.807C˃T
(=)ǂ / GH-secreting, prolactinoma, NFPA / N/A (3) / M, F, N/A / 10, 15, 50 / Tichomorowa, M.A. etal.6, Georgitsi, M. etal.10, Oriola, J. etal.12
Rare SNP
c.100–18C˃T
(?) / GH-secreting, prolactinoma / MA (2) / M (2) / 15, 35 / Tichomorowa, M.A. etal.6, Oriola, J. etal.12
c.47G˃A
(Arg16His) / GH-secreting, prolactinoma, ACTH-secreting, NFPA (2) / MI (2), G, N/A (2) / M (2), F, N/A (2) / 14, 20, 29, N/A (2) / Tichomorowa, M.A. etal.6, Cazabat, L. etal.9, Buchbinder, S. etal.16
c.355C˃T
(Arg119Trp) / GH-secreting / MA / F / 32 / Cai, F. etal.13
c.733G˃A
(Glu245Lys) / Prolactinoma / MA / F / 24 / Cai, F. etal.13
c.967C˃T
(Arg323Trp) / NFPA / MA / M / 41 / Cai, F. etal.13
The accession number used for the AIP transcript is NM_003977.2. *Translation stop codon.‡Mutation also found in patients with familial isolated pituitary adenoma.(=) Denotes silent change at protein level. Abbreviations: ACTH, adrenocorticotropic hormone; F, female; fs, frameshift; GA, giant adenoma (˃40mm in diameter); M, male; MA, macroadenoma; MI, microadenoma; N/A, not available; NFPA, nonfunctional pituitary adenoma.
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