SPRED1 Database

  • Reference sequences were NC_000015.9 and NM_152594.2. cDNA number 1 is the "A" of the start codon.
  • Frameshift is documented by the original amino acid followed by the codon number and "fs" (ex. Leu159 fs).
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Click for a detailed description of: NIH Diagnostic Criteria for NF1


164 variants found

Genomic Position Location Mutation Type Nucleotide Change Protein Change Classification Legius Syndrome Phenotype References Comments
Exon 1-7 Large deletion c.1-845-?_c.32+8517+?del p.0 Pathogenic Legius syndrome Messiaen  
Promoter-Exon 1 Large deletion c.1-?_c.32+? p.0 Pathogenic Multiple CALMs, mild learning disabilities; found in father who had multiple CALMs. Spencer (2011)
Promoter-Exon 4 Large deletion c.1-1175-?_c.423+19+?del p.? Pathogenic Legius syndrome Brems (2012)
Exon 1-7 Large deletion c.1-?_c.1335+? p.0 Pathogenic Multiple CALMs, speech delay and mild developmental delay. Spencer (2011)
Exon 1-7 Large deletion c.1-?_c.1335+? p.0 Pathogenic Multiple CALMs and axillary freckling. Spencer (2011)
Exon 1 Missense c.2T>C p.Met1? Uncertain Multiple CALMs, axillary and inguinal freckling, cephalalgia, learning disability, ADHD and developmental delay. Pasmant (2009)
Exon 1 Nonsense c.7G>T p.Glu3* Pathogenic Multiple CALMs and hyperactivity. Messiaen (2009)
Exon 1 Frameshift c.7_20delGAGGAGACGGCGAC p.Glu3Phefs*2 Pathogenic Multiple CALMs, axillary and inguinal freckling, head circumference in the 10-25th percentile. Messiaen (2009)
Exon 1 Frameshift c.18delG p.Thr7Leufs*15 Pathogenic Legius syndrome Pasmant
Exon 1 Frameshift c.22delT p.Ser8Leufs*14 Pathogenic Legius syndrome Messiaen  
Exon 1 Missense c.26A>T p.Asp9Val Uncertain Brems (2012)
Exon 1 Synonymous c.27C>T p.= Benign Multiple CALMs Trevisson  
Exon 1 Missense c.30C>A p.Asn10Lys Suspected Benign Brems (2012)
Exon 1 Splice Site c.32+2T>C p.? Pathogenic Multiple CALMs Messiaen  
Exon 2-4 Frameshift c.33-17014_423+568delins5 p.Asn12Profs*17 Pathogenic Legius syndrome Messiaen  
Exon 2-4 Deletion c.33-5928-?_c.423+19+?del p.Asn12Profs*17 Pathogenic Legius syndrome Messiaen
Exon 2-6 Frameshift c.33-20604_c.684+401delinsGAAA p.Asp11Glufs84 Pathogenic Multiple CALMs, bilateral axillary and inguinal freckling, ADHD and lipomas. Spencer (2011)
Exon 1 Synonymous c.42T>C p.= Benign Multiple CALMs, other small pigmented spots and axillary freckling. Messiaen (2009)
Exon 2 Synonymous c.42T>C p.= Uncertain Messiaen (2009)
Exon 2 Nonsense c.46C>T p.Arg16* Pathogenic Multiple CALMs and learning disability (Pasmant). Multiple CALMs and punctate freckling in groin (Spurlock). Pasmant (2009)
Exon 2 Nonsense c.52C>T p.Arg18* Pathogenic Multiple CALMs, thoracic freckling, head circumference in the 75-90th percentile, speech delay with normal intelligence, meatal stenosis, hypertelorism, mild hearing loss in left ear (Messiaen). Multiple CALMs, axillary and inguinal freckling, learning di Messiaen (2009)
Exon 2 Synonymous c.60G>C p.= Benign
Exon 2 Insertion c.60_61insC p.Val21Argfs*6 Pathogenic Multile CALMs, head circumference in the 50-75th percentile and hyperactivity. Messiaen (2009)
Exon 2 Nonsense c.70C>T p.Arg24* Pathogenic Multiple CALMs, mild to no freckling, head circumference percentile ranged from 3-97, lipomas, developmental delay and ADHD as well as one family member with cataract and another with eczema (Brems). Multiple CALMs, no other NF1 diagnostic signs (Spencer) Brems (2007)
Exon 2 Missense c.71G>A p.Arg24Gln Uncertain Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
Exon 2 Duplication c.87_88dupTG p.Gly30Valfs*11 Pathogenic Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
Exon 2 Missense c.88G>A p.Gly30Arg Uncertain Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
Exon 2 Missense c.91T>A p.Trp31Arg Uncertain Messiaen  
Exon 2 Missense c.92G>T p.Trp31Leu Uncertain Legius syndrome Messiaen  
Exon 2 Missense c.93G>T p.Trp31Cys Pathogenic Multiple CALMs, axillary freckling, developmental delay and ADHD. Denayer (2010)
Exon 2 Frameshift c.107_110delGGAG p.Gly36Valfs*3 Pathogenic Legius syndrome Messiaen  
Exon 2 Frameshift c.108delG p.Ser37Valfs*3 Pathogenic Legius syndrome Messiaen  
Exon 2 Missense c.124G>A p.Val42Ile Uncertain Legius syndrome and found in a patient with NF2 mutation (Spencer 2011). No signs of Legius syndrome; has acute myeloblastic leukaemia (Pasmant). Spencer (2011)
Exon 2 Missense c.131T>A p.Val44Asp Suspected Pathogenic Multiple CALMs, freckling and head circumference ranging from normal to 98th percentile. Spurlock (2009)
Exon 2 Nonsense c.148C>T p.Gln50* Pathogenic Brems (2012)  
Exon 2 Frameshift c.177delT p.Phe59Leufs*62 Pathogenic Mao et al, unpublished
Exon 2 Missense c.184G>C p.Gly62Arg Suspected Pathogenic Multiple CALMs. Mao et al, unpublished
Exon 2 Nonsense c.190C>T p.Arg64* Pathogenic Multiple CALMs (Brems). Mutation tracked with disease, multiple CALMs, macrocephaly, axillary and inguinal freckling, lipoma, learning disability and cephalalgia (Pasmant). Multiple CALMs, bilateral axillary freckling, head circumferences ranged from the Brems (2007)  
Exon 2 Missense c.191G>A p.Arg64Gln Uncertain
Intron 2 Frameshift c.207+1G>T p.Asp11Glufs*52 Pathogenic Legius syndrome Wimmer
Exon 3 Missense c.211G>A p.Val71Ile Uncertain
Exon 3 Nonsense c.217G>T p.Glu73* Pathogenic Multiple CALMs, head circumference in the 9th and 9oth percentile. Spurlock (2009)
Exon 3 Missense c.221G>T p.Cys74Phe Benign Multiple CALMs, freckling only in hyperpigmented quadrant, segmental pigmentary NF phenotype. Messiaen (2009)
Exon 3 Nonsense c.229A>T p.Lys77* Pathogenic Legius syndrome Messiaen  
Exon 3 Missense c.239T>G p.Leu80Arg Uncertain Multiple CALMs. Spencer (2011)
Exon 3 Frameshift c.242_256delTTTATAATAAGGTCA p.Ile81_Val85del Pathogenic Multiple CALMs (Brems). Multiple CALMs, some axillary and inguinal pigmentation, head circumference in the 60th percentile, normal brain MRI and pectus excavatum (Messiaen 2009). Brems (2007)
Exon 3 Missense c.263C>A p.Thr88Lys Uncertain Legius syndrome Pasmant  
Exon 3 Frameshift c.269delA p.His90Profs*31 Pathogenic Brems (2012)  
Exon 3 Missense c.270C>G p.His90Gln Uncertain NF1 Messiaen
Exon 3 Frameshift c.271delC p.His91Thrfs*30 Pathogenic Multiple CALMs. Messiaen (2009)  
Exon 3 Missense c.274T>C p.Trp92Arg Uncertain Legius syndrome Messiaen  
Exon 3 Frameshift c.283delG p.Asp95Metfs*26 Pathogenic Legius syndrome Messiaen  
Exon 3 Synonymous c.291G>A p.= Benign Muram-Zborovski (2010)
Exon 3 Missense c.299G>A p.Gly100Asp Uncertain Not given. Brems (2012)
Exon 3 Frameshift c.303dupT p.Thr102Asnfs*7 Pathogenic Legius syndrome Denayer (2010)  
Exon 3 Frameshift c.304dupA p.Thr102Asnfs*7 Pathogenic Multiple CALMs (Brems). Multiple CALMs and learning difficulties (Denayer). Brems (2007)
Exon 3 Frameshift c.305delC p.Thr102Serfs*19 Pathogenic Multiple CALMs. Spencer (2011)  
Exon 3 Missense c.305C>G p.Thr102Arg Pathogenic Multiple CALMs, some axilary and inguinal freckling, head circumferences ranging from the 25-75th percentile. Messiaen (2009)
Exon 3 Missense c.305C>A p.Thr102Lys Suspected pathogenic Legius syndrome. Spencer (2011)
Exon 3 Missense c.305C>T p.Thr102Met Suspected pathogenic Legius syndrome. Spencer (2011)
Exon 3 Frameshift c.320_333delCTGATGCTAGGGCT p.Ala107Valfs*2 Pathogenic Multiple CALMs, axillary/inguinal freckling and head circumferences ranging from 50th to greater than the 97th percentile. Messiaen (2009)
Exon 3 Frameshift c.326_329dupCTAG p.Ala110Serfs*2 Pathogenic Multiple CALMs (Messiaen). Multiple CALMs, axillary freckling, ADHD (Denayer 2010). Messiaen (2009)
Exon 3 Frameshift c.331dupG p.Ala111fs Pathogenic Legius syndrome Pasmant 2014
Exon 3 Frameshift c.340dupA p.Arg114Lysfs*20 Pathogenic Multiple CALMs, learning dificulties Denayer (2010)
Exon 3 Missense c.347T>A p.Ile116Asn Uncertain Legius syndrome Messiaen
Exon 3 Nonsense c.349C>T p.Arg117* Pathogenic Multiple CALMs, lipomas, and head circumference percentile ranging from 25-97. Multiple CALMs and developmental delay (Denayer). Brems (2007)
Exon 3 Missense c.353G>A p.Arg118Lys Uncertain
Exon 3 Frameshift c.360dupA p.Glu121Argfs*13 Pathogenic Multiple CALMs and learning disability. Denayer (2010)
Exon 3 Frameshift c.361delG p.Gly121Argfs*13 Pathogenic Legius syndrome Messiaen  
Exon 3 Frameshift c.375delA p.Gln125fs Pathogenic Legius syndrome Pasmant (2014)  
Intron 3 Intronic c.377-10A>G p.? Benign
Intron 3 Intronic c.377-9T>G p.? Suspected Pathogenic Legius syndrome Van Minkelen  
Intron 3 Splice Site c.377-2A>C p.Cys127Lysfs*2 Pathogenic Legius syndrome Brems (2012)
Exon 4 Nonsense c.381C>A p.Cys127* Pathogenic Legius syndrome Pasamant
Exon 4 Nonsense c.389C>A p.Ser130* Pathogenic Legius syndrome Pasamant
Exon 4 Nonsense c.389C>G p.Ser130* Pathogenic Legius syndrome Pasmant (2014)  
Exon 4 Frameshift c.395dupA p.Asn132Lysfs*2 Pathogenic Legius syndrome, with typical CALMs, axillary freckling, learning disabilities. B-cell acute lymphoblastic leukaemia Pasmant (2014)
Intron 4 Splice Site c.423+1G>A p.Cys127Lysfs*2 Uncertain Multiple CALMs, varying degrees of freckling, head circumference percentile ranged from 50-97 and learning difficulty. Brems (2007)
Intron 4 Splice Site c.423+5G>A c.Cys124Glnfs*10 Pathogenic Legius syndrome Messiaen
Intron 4 Intronic c.424-8C>A p.? Benign Muram-Zborovski (2010)
Exon 5 Synonymous c.426A>G p.= Uncertain Messiaen
Exon 5 Missense c.446G>A p.Ser149Asn Benign Multiple CALMs (Brems and Messiaen). Brems (2007)
Exon 5 Frameshift c.460_463dupGATC p.His155Argfs*13 Pathogenic Brems (2012)  
Exon 5 Frameshift c.468_469insGA p.Phe157Aspfs*18 Pathogenic Multiple CALMs. Spencer (2011)  
Exon 5 Frameshift c.468_469insCA p.Phe157fs Pathogenic Multiple CALMs. Messiaen (2009)
Exon 5 Nonsense c.475C>T p.Gln159* Pathogenic Brems (2012)  
Exon 5 Deletion c.493delA p.Ser165Valfs*9 Pathogenic Multiple CALMs. Spencer (2011)  
Exon 5 Missense c.511T>C p.Ser171Pro Uncertain Messiaen
Exon 5 Missense c.525G>A p.Glu179Lys Uncertain
Exon 5 Missense c.563T>C p.Met188Thr Uncertain
Exon 5 Missense c.564G>A p.Met188Ile Benign Multiple CALMs. Messiaen (2009)
Exon 5 Frameshift c.576_580dupCAATC p.Gln194Profs*4 Pathogenic Multiple CALMs, axillary freckling and mild learning disability. Denayer (2010)
Exon 5 Nonsense c.580C>T p.Gln194* Pathogenic Multiple CALMs, axillary and inguinal freckling, learning disabilities and head circumference: greater than 98th percentile. Muram-Zborovski (2010)
Exon 6-7 Deletion c.583-2841-?_c.*80+?del p.? Pathogenic Legius syndrome Messiaen
Intron 5 Intronic c.583-7A>G p.? Benign
Exon 6 Missense c.587C>T p.Thr196Ile Benign Multiple CALMs (Spencer). Multiple CALMs and abnormal development (Messiaen). Messiaen (2009)
Exon 6 Nonsense c.605T>A p.Leu202* Pathogenic Multiple CALMs. Messiaen (2009)
Exon 6 Missense c.607G>A p.Asp203Asn Uncertain
Exon 6 Synonymous c.619A>C p.= Benign
Exon 6 Synonymous c.633C>T p.= Benign
Exon 6 Missense c.634G>A p.Val212Ile Uncertain Multiple CALMs. Spencer (2011)
Exon 6 Nonsense c.637C>T p.Gln213* Pathogenic Multiple CALMs, axillary and inguinal freckling and learning disability. Pasmant (2009)
Exon 6 Missense c.640C>T p.Arg214Trp Uncertain
Exon 6 Missense c.643C>G p.Gln215Glu Uncertain
Exon 6 Nonsense c.643C>T p.Gln215* Pathogenic Multiple CALMs and lipomas. Brems (2007)
Exon 6 Missense c.645A>C p.Gln215His Uncertain
Exon 6 Missense c.667delC p.Leu223* Pathogenic Multiple CALMs. Spencer (2011)  
Exon 6 Frameshift c.673delT p.Ser225Profs*7 Pathogenic Messiaen  
Exon 6 Missense c.674C>T p.Ser225Phe Uncertain No signs of Legius syndrome; has B-cell acute lymphoblastic leukaemia Pasmant (2014)
Exon 6 Synonymous c.675C>T p.= Benign Messiaen
Intron 6 Intronic c.685-15C>G p.? Uncertain
Intron 6 Intronic c.685-7T>C p.? Uncertain
Exon 7 Synonymous c.687C>A p.= Uncertain
Exon 7 Missense c.698C>A p.Ser233* Pathogenic Legius syndrome Messiaen
Exon 7 Frameshift c.700dupA p.Ile234Asnfs*9 Pathogenic Not given Leiden Database (LOVD)  
Exon 7 Frameshift c.700_703delATCA p.Ile234Aspfs*14 Pathogenic Multiple CALMs and head circumference: greater than 95th percentile. Messiaen (2009)
Exon 7 Missense c.702C>G p.Ile243Met Uncertain
Exon 7 Missense c.767G>A p.Arg256His Uncertain Five month old with CALMs and hypopigmentation (database submission). Brems (2012)
Exon 7 Missense c.769C>T p.Arg257Cys Uncertain Legius syndrome Brems (2012)
Exon 7 Frameshift c.781delT p.? Pathogenic Multiple CALMs and Crowe sign. Lopez (2011)
Exon 7 Nonsense c.784A>T p.Arg262* Pathogenic Multiple CALMs, axillary and inguinal freckling. Spurlock (2009)
Exon 7 Frameshift c.796_797delAT p.Met266Valfs*4 Pathogenic Multiple CALMs. Brems (2007)
Exon 7 Missense c.821A>G p.Asp274Gly SuspectedBenign Brems (2012)
Exon 7 Frameshift c.832dupT p.Ser278Phefs*7 Pathogenic Brems (2012)  
Exon 7 Missense c.866A>C p.Lys289Thr Uncertain
Exon 7 Frameshift c.923_924delCT p.Ser308Cysfs*4 Pathogenic Multiple CALMs, head circumference: 25-50th and 97th percentile. Messiaen (2009)
Exon 7 Missense c.926T>C p.Val309Ala Benign Multiple CALMs. Spencer (2011)
Exon 7 Missense c.931T>C p.Phe311Leu Uncertain Messiaen
Exon 7 Missense c.938C>T p.Thr313Met Benign Multiple CALMs. Messiaen (2009)
Exon 7 Synonymous c.939G>A p.= Benign
Exon 7 Nonsense c.940C>T p.Gln314* Pathogenic Multiple CALMs, axillary and inguinal freckling, macrocephaly and mild learning disability. Denayer (2010)
Exon 7 Missense c.944C>T p.Pro315Leu SuspectedBenign Brems (2012)
Exon 7 Synonymous c.963G>A p.= Benign
Exon 7 Nonsense c.964A>T p.Lys322* Pathogenic Multiple CALMs, head circumferences: greater than 97th, 97th and 90-97th percentile (Messiaen 2009). Brems (2007)
Exon 7 Nonsense c.973C>T p.Arg325* Pathogenic Multiple CALMs and family history or CALMS (Brems). Multiple CALMs, axillary and inguinal freckling, head circumferences: 10th, 25-50th percentile, abnormal development: special education and ADHD and language delay (Messian). Brems (2007)
Exon 7 Frameshift c.989delG p.Gly330Valfs*76 Pathogenic Brems (2012)  
Exon 7 Nonsense c.991G>T p.Glu331* Pathogenic Multiple CALMs. Spencer (2011)  
Exon 7 Missense c.1001G>A p.Arg334His Uncertain
Exon 7 Missense c.1006G>A p.Val336Ile Uncertain
Exon 7 Missense c.1031A>G p.His344Arg Uncertain Multiple CALMs. Spencer (2011)
Exon 7 Synonymous c.1044T>C p.Val348Val Benign Muram-Zborovski (2010)
Exon 7 Frameshift c.1045_1046delAG p.Arg349Glyfs*11 Pathogenic Multiple CALMs, general and inguinal freckling, macrocephaly, suspected autism. Denayer (2010)
Exon 7 Frameshift c.1048_1049delGG p.Gly350Lysfs*10 Pathogenic Multiple CALMs and freckling. Spurlock (2009)
Exon 7 Frameshift c.1048_1060del p.Gly350Metfs*52 Pathogenic Multiple CALMs, diffuse freckling (Pasamant). Multiple CALMs, macrocephaly, ADHD and lipomas (Denayer). Pasmant (2009)
Exon 7 Frameshift c.1149_1152delAGAG p.Gly350Aspfs*55 Pathogenic Multiple CALMs (Brems). Multiple CALMs without freckling (Spurlock). Multiple CALMs, axillary and inguinal freckling, head circumferences: 90-97th and 50th percentile; also found, angiolipoma (Messiaen). Multiple CALMs, axillary and inguinal freckling (De Brems (2007)
Exon 7 Missense c.1078A>G p.Lys360Glu Uncertain
Exon 7 Frameshift c.1073delC p.Pro358Leufs*48 Pathogenic Multiple CALMs. Spencer (2011)
Exon 7 Missense c.1089G>A p.Ile363Met Uncertain No signs of Legius syndrome; has B-cell acute lymphoblastic leukaemia Pasmant (2014)
Exon 7 Missense c.1096G>A p.Val366Ile Uncertain
Exon 7 Deletion c.1155del p.Gly385Ile*20 Pathogenic Legius syndrome Brems (2013)
Exon 7 Missense c.1192G>A p.Asp398Asn Benign Multiple CALMs (Spencer 2011). Multiple CALMs and hyperactivity (Messiaen). Messiaen (2009)
Exon 7 Frameshift c.1204_1207dupTTGC p.Arg403Leufs*30 Pathogenic Multiple CALMs and head circumference 90th percentile. Messiaen (2009)
Exon 7 Missense c.1222G>T p.Val408Leu Uncertain
Exon 7 Missense c.1223T>A p.Val408Glu Uncertain Brems (2012)
Exon 7 Missense c.1243C>G p.Pro415Ala Pathogenic Multiple CALMs, axillary pigmentation, head circumferences: 20th and 75th percentile, language delay and fine motor delay. Messiaen (2009)
Exon 7 Missense c.1246C>T p.Cys416Arg Uncertain Multiple CALMs. Spencer (2011)
Exon 7 Frameshift c.1248dupT p.Met417Tyrfs*15 Suspected Pathogenic Multiple CALMs and inguinal freckling. Messiaen (2009)
Exon 7 frameshift c.1252delT p.Cys418Alafs*6 Pathogenic Multiple CALMs (Spencer). Multiple CALMs, axillary and inguinal freckling, head circumferences: much greater than 97th and 90-95th percentile, language delay and developmental delay, seizures and one patient with unequal gluteal folds (Messiaen). Messiaen (2009)
Exon 7 Synonymous c.1260C>T p.= Benign
Exon 7 Missense c.1273A>G p.Met425Val Uncertain Legius syndrome Brems (2012)
Exon 7 Missense c.1283G>A p.Arg428His Uncertain
Exon 7 Missense c.1289G>C p.Gly430Ala Uncertain Brems (2012)
Exon 7 Frameshift c.1289_1298del p.Gly430Valfs*29 Uncertain Brems (2012)
Exon 7 Missense c.1298G>A p.Cys433Tyr Benign Messiaen (2009)