c.1A>G
|
Initiation codon mutation
|
Pathogenic
|
(55. Madeira JL, Nishi MY, Nakaguma M, Benedetti AF, Biscotto IP, Fernandes T, et al. Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations. Clin Endocrinol (Oxf). 2017;87(6):725-32.)
|
c.2T>C |
Initiation codon mutation |
Pathogenic |
(2828. Lemos MC, Gomes L, Bastos M, Leite V, Limbert E, Carvalho D, et al. PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency. Clin Endocrinol (Oxf). 2006;65(4): 479-85.) |
c.46C>T |
p.Arg16Ter |
Pathogenic |
(4040. Birla S, Khadgawat R, Jyotsna VP, Jain V, Garg MK, Bhalla AS, et al. Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency. Horm Metab Res. 2016;48(12):822-7.) |
c.109+1G>A
|
Splicing site change
|
Pathogenic
|
(55. Madeira JL, Nishi MY, Nakaguma M, Benedetti AF, Biscotto IP, Fernandes T, et al. Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations. Clin Endocrinol (Oxf). 2017;87(6):725-32.)
|
c.109+1G>T |
Splicing site change |
Pathogenic |
(2828. Lemos MC, Gomes L, Bastos M, Leite V, Limbert E, Carvalho D, et al. PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency. Clin Endocrinol (Oxf). 2006;65(4): 479-85.) |
c.109+2T>G |
Splicing site change |
Pathogenic |
(1313. Cogan JD, Wu W, Phillips JA 3rd, Arnhold IJ, Agapito A, Fofanova OV, et al. The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab. 1998;83(9):3346-9.) |
c.112_124del |
p.Ser38Profs*123 |
Pathogenic |
(4141. Fofanova O, Takamura N, Kinoshita E, Parks JS, Brown MR, Peterkova VA, et al. Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency. J Clin Endocrinol Metab. 1998;83(7):2601-4.) |
c.149_150delGA |
p.Gly52Aspfs*58 |
Pathogenic |
(4242. Tatsumi KI, Kikuchi K, Tsumura K, Amino N. A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency. Clin Endocrinol (Oxf). 2004;61(5):635-40.) |
c.150delA
|
p.Arg53Aspfs*112
|
Pathogenic
|
(3636. Krzisnik CK, Kolacio Z, Battelino T, Brown M, Parks JS, Laron Z. The “little people” of the island of Krk - revisited. Etiology of hypopituitarism revealed. J Endocr Genet. 1999;1:9-19.)
|
c.157delA |
p.Arg53Aspfs*112 |
Pathogenic |
(4242. Tatsumi KI, Kikuchi K, Tsumura K, Amino N. A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency. Clin Endocrinol (Oxf). 2004;61(5):635-40.) |
c.211C>T |
p.Arg71Cys |
VUS |
(4343. Reynaud R, Chadli-Chaieb M, Vallette-Kasic S, Barlier A, Sarles J, Pellegrini-Bouiller I, et al. A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies. J Clin Endocrinol Metab. 2004;89(11):5779-86.) |
c.212G>A |
p.Arg71His |
VUS |
(4343. Reynaud R, Chadli-Chaieb M, Vallette-Kasic S, Barlier A, Sarles J, Pellegrini-Bouiller I, et al. A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies. J Clin Endocrinol Metab. 2004;89(11):5779-86.) |
c.217C>T |
p.Arg73Cys |
Pathogenic |
(1212. Duquesnoy P, Roy A, Dastot F, Ghali I, Teinturier C, Netchine I, et al. Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency. FEBS Lett. 1998;437(3):216-20.,4444. Voutetakis A, Maniati-Christidi M, Kanaka-Gantenbein C, Dracopoulou M, Argyropoulou M, Livadas S, et al. Prolonged jaundice and hypothyroidism as the presenting symptoms in a neonate with a novel Prop1 gene mutation (Q83X). Eur J Endocrinol. 2004;150(3):257-64.) |
c.218G>A
|
p.Arg73His
|
Pathogenic
|
(4545. Vallette-Kasic S, Barlier A, Teinturier C, Diaz A, Manavela M, Berthezène F, et al. PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency. J Clin Endocrinol Metab. 2001;86(9):4529-35.)
|
c.247C>T |
p.Gln83Ter |
Pathogenic |
(4646. Parks JS, Brown MR, Hurley DL, Phelps CJ, Wajnrajch MP. Heritable disorders of pituitary development. J Clin Endocrinol Metab. 1999;84(12):4362-70.) |
c.263T>C
|
p.Phe88Ser
|
Pathogenic
|
(44. Osorio MG, Kopp P, Marui S, Latronico AC, Mendonca BB, Arnhold IJ. Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1. J Clin Endocrinol Metab. 2000;85(8):2779-85.)
|
c.295C>T |
p.Arg99Ter |
Pathogenic |
(4747. Vieira TC, Dias da Silva MR, Cerutti JM, Brunner E, Borges M, Arnaldi LT, et al. Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of Prophet of Pit-1 presenting as constitutional growth delay. J Clin Endocrinol Metab. 2003;88(1):38-44.) |
c.296G>A |
p.Arg99Gln |
Likely pathogenic |
(4848. Kelberman D, Turton JP, Woods KS, Mehta A, Al-Khawari M, Greening J, et al. Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD). Clin Endocrinol (Oxf). 2009;70(1):96-103.) |
c.301_302delAG
|
p.Leu102Cysfs*8
|
Pathogenic
|
(11. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O’Connell SM, et al. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. 1998;18(2):147-9.)
|
c.310delC |
p.Arg104Glyfs*61 |
Pathogenic |
(4949. Ogo A, Maruta T, Ide C, Sakai Y, Matoba Y, Hiramatsu S, et al. Recombinant human growth hormone replacement in a Japanese man with a novel PROP1 gene mutation (R112X). Fukuoka Igaku Zasshi. 2011;102(9):277-83.) |
c.334C>T |
p.Arg112Ter |
Pathogenic |
(5050. Avbelj Stefanija M, Kotnik P, Bratanic N, Zerjav Tansek M, Bertok S, Bratina N, et al. Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency. Horm Res Paediatr. 2015;84(3):153-8.) |
c.342+1G>C
|
Splicing site change
|
Pathogenic
|
(55. Madeira JL, Nishi MY, Nakaguma M, Benedetti AF, Biscotto IP, Fernandes T, et al. Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations. Clin Endocrinol (Oxf). 2017;87(6):725-32.)
|
c.343-11C>G |
Splicing site change |
Likely pathogenic |
(4949. Ogo A, Maruta T, Ide C, Sakai Y, Matoba Y, Hiramatsu S, et al. Recombinant human growth hormone replacement in a Japanese man with a novel PROP1 gene mutation (R112X). Fukuoka Igaku Zasshi. 2011;102(9):277-83.) |
c.343-2A>T |
Splicing site change |
Pathogenic |
(1212. Duquesnoy P, Roy A, Dastot F, Ghali I, Teinturier C, Netchine I, et al. Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency. FEBS Lett. 1998;437(3):216-20.) |
c.349T>A |
p.Phe117Ile |
Pathogenic |
(11. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O’Connell SM, et al. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. 1998;18(2):147-9.) |
c.358C>T |
p.Arg120Cys |
Pathogenic |
(11. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O’Connell SM, et al. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. 1998;18(2):147-9.) |
c.362G>C |
p.Arg121Thr |
VUS |
(5151. Nose O, Tatsumi K, Nakano Y, Amino N. Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT). J Pediatr Endocrinol Metab. 2006;19(4):491-8.) |
c.373C>T |
p.Arg125Trp |
Pathogenic |
(4949. Ogo A, Maruta T, Ide C, Sakai Y, Matoba Y, Hiramatsu S, et al. Recombinant human growth hormone replacement in a Japanese man with a novel PROP1 gene mutation (R112X). Fukuoka Igaku Zasshi. 2011;102(9):277-83.) |
c.467insT |
p.Tyr157Leufs*36 |
Pathogenic |
(5252. Shibahara H, Ikeshita N, Sugiyama Y, Toda K, Yamamoto D, Herningtyas EH, et al. W194XProp1 and S156insTProp1, both of which have intact DNA-binding domain, show a different DNA-binding activity to the Prop1-binding element in human Pit-1 gene. Mol Cell Endocrinol. 2010;323(2):167-71.,5353. Reynaud R, Barlier A, Vallette-Kasic S, Saveanu A, Guillet MP, Simonin G, et al. An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain. J Clin Endocrinol Metab. 2005;90(8):4880-7.) |
c.582G>A |
p.Trp194Ter |
Pathogenic |
(5353. Reynaud R, Barlier A, Vallette-Kasic S, Saveanu A, Guillet MP, Simonin G, et al. An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain. J Clin Endocrinol Metab. 2005;90(8):4880-7.,5454. Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, Brue T, et al. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91(9):3329-36.) |
c.629delC |
p.Pro210Hisfs*25 (prolonged protein) |
Pathogenic |
(5454. Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, Brue T, et al. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91(9):3329-36.) |