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
38544542 Exon 1-7 Large deletion c.1-845-?_c.32+8517+?del p.0 Pathogenic Legius syndrome Messiaen  
38545386 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)
38545386 Promoter-Exon 4 Large deletion c.1-1175-?_c.423+19+?del p.? Pathogenic Legius syndrome Brems (2012)
38545386 Exon 1-7 Large deletion c.1-?_c.1335+? p.0 Pathogenic Multiple CALMs, speech delay and mild developmental delay. Spencer (2011)
38545386 Exon 1-7 Large deletion c.1-?_c.1335+? p.0 Pathogenic Multiple CALMs and axillary freckling. Spencer (2011)
38545390 Exon 1 Missense c.2T>C p.Met1? Uncertain Multiple CALMs, axillary and inguinal freckling, cephalalgia, learning disability, ADHD and developmental delay. Pasmant (2009)
38545393 Exon 1 Nonsense c.7G>T p.Glu3* Pathogenic Multiple CALMs and hyperactivity. Messiaen (2009)
38545393 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)
38545404 Exon 1 Frameshift c.18delG p.Thr7Leufs*15 Pathogenic Legius syndrome Pasmant
38545408 Exon 1 Frameshift c.22delT p.Ser8Leufs*14 Pathogenic Legius syndrome Messiaen  
38545412 Exon 1 Missense c.26A>T p.Asp9Val Uncertain Brems (2012)
38545413 Exon 1 Synonymous c.27C>T p.= Benign Multiple CALMs Trevisson  
38545416 Exon 1 Missense c.30C>A p.Asn10Lys Suspected Benign Brems (2012)
38545420 Exon 1 Splice Site c.32+2T>C p.? Pathogenic Multiple CALMs Messiaen  
38574560 Exon 2-4 Frameshift c.33-17014_423+568delins5 p.Asn12Profs*17 Pathogenic Legius syndrome Messiaen  
38585646 Exon 2-4 Deletion c.33-5928-?_c.423+19+?del p.Asn12Profs*17 Pathogenic Legius syndrome Messiaen
38591574 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)
38591583 Exon 1 Synonymous c.42T>C p.= Benign Multiple CALMs, other small pigmented spots and axillary freckling. Messiaen (2009)
38591583 Exon 2 Synonymous c.42T>C p.= Uncertain Messiaen (2009)
38591587 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)
38591593 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)
38591601 Exon 2 Synonymous c.60G>C p.= Benign
38591601 Exon 2 Insertion c.60_61insC p.Val21Argfs*6 Pathogenic Multile CALMs, head circumference in the 50-75th percentile and hyperactivity. Messiaen (2009)
38591611 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)
38591612 Exon 2 Missense c.71G>A p.Arg24Gln Uncertain Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
38591628 Exon 2 Duplication c.87_88dupTG p.Gly30Valfs*11 Pathogenic Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
38591629 Exon 2 Missense c.88G>A p.Gly30Arg Uncertain Multiple CALMs, no other NF1 diagnostic signs. Spencer (2011)
38591632 Exon 2 Missense c.91T>A p.Trp31Arg Uncertain Messiaen  
38591633 Exon 2 Missense c.92G>T p.Trp31Leu Uncertain Legius syndrome Messiaen  
38591634 Exon 2 Missense c.93G>T p.Trp31Cys Pathogenic Multiple CALMs, axillary freckling, developmental delay and ADHD. Denayer (2010)
38591648 Exon 2 Frameshift c.107_110delGGAG p.Gly36Valfs*3 Pathogenic Legius syndrome Messiaen  
38591649 Exon 2 Frameshift c.108delG p.Ser37Valfs*3 Pathogenic Legius syndrome Messiaen  
38591665 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)
38591672 Exon 2 Missense c.131T>A p.Val44Asp Suspected Pathogenic Multiple CALMs, freckling and head circumference ranging from normal to 98th percentile. Spurlock (2009)
38591689 Exon 2 Nonsense c.148C>T p.Gln50* Pathogenic Brems (2012)  
38591718 Exon 2 Frameshift c.177delT p.Phe59Leufs*62 Pathogenic Mao et al, unpublished
38591725 Exon 2 Missense c.184G>C p.Gly62Arg Suspected Pathogenic Multiple CALMs. Mao et al, unpublished
38591731 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)  
38591732 Exon 2 Missense c.191G>A p.Arg64Gln Uncertain
38591749 Intron 2 Frameshift c.207+1G>T p.Asp11Glufs*52 Pathogenic Legius syndrome Wimmer
38614445 Exon 3 Missense c.211G>A p.Val71Ile Uncertain
38614451 Exon 3 Nonsense c.217G>T p.Glu73* Pathogenic Multiple CALMs, head circumference in the 9th and 9oth percentile. Spurlock (2009)
38614454 Exon 3 Missense c.221G>T p.Cys74Phe Benign Multiple CALMs, freckling only in hyperpigmented quadrant, segmental pigmentary NF phenotype. Messiaen (2009)
38614463 Exon 3 Nonsense c.229A>T p.Lys77* Pathogenic Legius syndrome Messiaen  
38614473 Exon 3 Missense c.239T>G p.Leu80Arg Uncertain Multiple CALMs. Spencer (2011)
38614476 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)
38614497 Exon 3 Missense c.263C>A p.Thr88Lys Uncertain Legius syndrome Pasmant  
38614503 Exon 3 Frameshift c.269delA p.His90Profs*31 Pathogenic Brems (2012)  
38614504 Exon 3 Missense c.270C>G p.His90Gln Uncertain NF1 Messiaen
38614505 Exon 3 Frameshift c.271delC p.His91Thrfs*30 Pathogenic Multiple CALMs. Messiaen (2009)  
38614508 Exon 3 Missense c.274T>C p.Trp92Arg Uncertain Legius syndrome Messiaen  
38614517 Exon 3 Frameshift c.283delG p.Asp95Metfs*26 Pathogenic Legius syndrome Messiaen  
38614525 Exon 3 Synonymous c.291G>A p.= Benign Muram-Zborovski (2010)
38614533 Exon 3 Missense c.299G>A p.Gly100Asp Uncertain Not given. Brems (2012)
38614537 Exon 3 Frameshift c.303dupT p.Thr102Asnfs*7 Pathogenic Legius syndrome Denayer (2010)  
38614538 Exon 3 Frameshift c.304dupA p.Thr102Asnfs*7 Pathogenic Multiple CALMs (Brems). Multiple CALMs and learning difficulties (Denayer). Brems (2007)
38614539 Exon 3 Frameshift c.305delC p.Thr102Serfs*19 Pathogenic Multiple CALMs. Spencer (2011)  
38614539 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)
38614540 Exon 3 Missense c.305C>A p.Thr102Lys Suspected pathogenic Legius syndrome. Spencer (2011)
38614541 Exon 3 Missense c.305C>T p.Thr102Met Suspected pathogenic Legius syndrome. Spencer (2011)
38614554 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)
38614560 Exon 3 Frameshift c.326_329dupCTAG p.Ala110Serfs*2 Pathogenic Multiple CALMs (Messiaen). Multiple CALMs, axillary freckling, ADHD (Denayer 2010). Messiaen (2009)
38614565 Exon 3 Frameshift c.331dupG p.Ala111fs Pathogenic Legius syndrome Pasmant 2014
38614574 Exon 3 Frameshift c.340dupA p.Arg114Lysfs*20 Pathogenic Multiple CALMs, learning dificulties Denayer (2010)
38614581 Exon 3 Missense c.347T>A p.Ile116Asn Uncertain Legius syndrome Messiaen
38614583 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)
38614587 Exon 3 Missense c.353G>A p.Arg118Lys Uncertain
38614594 Exon 3 Frameshift c.360dupA p.Glu121Argfs*13 Pathogenic Multiple CALMs and learning disability. Denayer (2010)
38614595 Exon 3 Frameshift c.361delG p.Gly121Argfs*13 Pathogenic Legius syndrome Messiaen  
38614609 Exon 3 Frameshift c.375delA p.Gln125fs Pathogenic Legius syndrome Pasmant (2014)  
38616954 Intron 3 Intronic c.377-10A>G p.? Benign
38616955 Intron 3 Intronic c.377-9T>G p.? Suspected Pathogenic Legius syndrome Van Minkelen  
38616962 Intron 3 Splice Site c.377-2A>C p.Cys127Lysfs*2 Pathogenic Legius syndrome Brems (2012)
38616968 Exon 4 Nonsense c.381C>A p.Cys127* Pathogenic Legius syndrome Pasamant
38616976 Exon 4 Nonsense c.389C>A p.Ser130* Pathogenic Legius syndrome Pasamant
38616976 Exon 4 Nonsense c.389C>G p.Ser130* Pathogenic Legius syndrome Pasmant (2014)  
38616982 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)
38617011 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)
38617015 Intron 4 Splice Site c.423+5G>A c.Cys124Glnfs*10 Pathogenic Legius syndrome Messiaen
38631930 Intron 4 Intronic c.424-8C>A p.? Benign Muram-Zborovski (2010)
38631940 Exon 5 Synonymous c.426A>G p.= Uncertain Messiaen
38631960 Exon 5 Missense c.446G>A p.Ser149Asn Benign Multiple CALMs (Brems and Messiaen). Brems (2007)
38631974 Exon 5 Frameshift c.460_463dupGATC p.His155Argfs*13 Pathogenic Brems (2012)  
38631982 Exon 5 Frameshift c.468_469insGA p.Phe157Aspfs*18 Pathogenic Multiple CALMs. Spencer (2011)  
38631983 Exon 5 Frameshift c.468_469insCA p.Phe157fs Pathogenic Multiple CALMs. Messiaen (2009)
38631989 Exon 5 Nonsense c.475C>T p.Gln159* Pathogenic Brems (2012)  
38632007 Exon 5 Deletion c.493delA p.Ser165Valfs*9 Pathogenic Multiple CALMs. Spencer (2011)  
38632025 Exon 5 Missense c.511T>C p.Ser171Pro Uncertain Messiaen
38632049 Exon 5 Missense c.525G>A p.Glu179Lys Uncertain
38632077 Exon 5 Missense c.563T>C p.Met188Thr Uncertain
38632078 Exon 5 Missense c.564G>A p.Met188Ile Benign Multiple CALMs. Messiaen (2009)
38632090 Exon 5 Frameshift c.576_580dupCAATC p.Gln194Profs*4 Pathogenic Multiple CALMs, axillary freckling and mild learning disability. Denayer (2010)
38632094 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)
38638782 Exon 6-7 Deletion c.583-2841-?_c.*80+?del p.? Pathogenic Legius syndrome Messiaen
38641616 Intron 5 Intronic c.583-7A>G p.? Benign
38641627 Exon 6 Missense c.587C>T p.Thr196Ile Benign Multiple CALMs (Spencer). Multiple CALMs and abnormal development (Messiaen). Messiaen (2009)
38641645 Exon 6 Nonsense c.605T>A p.Leu202* Pathogenic Multiple CALMs. Messiaen (2009)
38641647 Exon 6 Missense c.607G>A p.Asp203Asn Uncertain
38641659 Exon 6 Synonymous c.619A>C p.= Benign
38641673 Exon 6 Synonymous c.633C>T p.= Benign
38641674 Exon 6 Missense c.634G>A p.Val212Ile Uncertain Multiple CALMs. Spencer (2011)
38641677 Exon 6 Nonsense c.637C>T p.Gln213* Pathogenic Multiple CALMs, axillary and inguinal freckling and learning disability. Pasmant (2009)
38641680 Exon 6 Missense c.640C>T p.Arg214Trp Uncertain
38641683 Exon 6 Missense c.643C>G p.Gln215Glu Uncertain
38641683 Exon 6 Nonsense c.643C>T p.Gln215* Pathogenic Multiple CALMs and lipomas. Brems (2007)
38641685 Exon 6 Missense c.645A>C p.Gln215His Uncertain
38641707 Exon 6 Missense c.667delC p.Leu223* Pathogenic Multiple CALMs. Spencer (2011)  
38641713 Exon 6 Frameshift c.673delT p.Ser225Profs*7 Pathogenic Messiaen  
38641714 Exon 6 Missense c.674C>T p.Ser225Phe Uncertain No signs of Legius syndrome; has B-cell acute lymphoblastic leukaemia Pasmant (2014)
38641715 Exon 6 Synonymous c.675C>T p.= Benign Messiaen
38643200 Intron 6 Intronic c.685-15C>G p.? Uncertain
38643208 Intron 6 Intronic c.685-7T>C p.? Uncertain
38643217 Exon 7 Synonymous c.687C>A p.= Uncertain
38643228 Exon 7 Missense c.698C>A p.Ser233* Pathogenic Legius syndrome Messiaen
38643230 Exon 7 Frameshift c.700dupA p.Ile234Asnfs*9 Pathogenic Not given Leiden Database (LOVD)  
38643230 Exon 7 Frameshift c.700_703delATCA p.Ile234Aspfs*14 Pathogenic Multiple CALMs and head circumference: greater than 95th percentile. Messiaen (2009)
38643232 Exon 7 Missense c.702C>G p.Ile243Met Uncertain
38643297 Exon 7 Missense c.767G>A p.Arg256His Uncertain Five month old with CALMs and hypopigmentation (database submission). Brems (2012)
38643299 Exon 7 Missense c.769C>T p.Arg257Cys Uncertain Legius syndrome Brems (2012)
38643311 Exon 7 Frameshift c.781delT p.? Pathogenic Multiple CALMs and Crowe sign. Lopez (2011)
38643314 Exon 7 Nonsense c.784A>T p.Arg262* Pathogenic Multiple CALMs, axillary and inguinal freckling. Spurlock (2009)
38643326 Exon 7 Frameshift c.796_797delAT p.Met266Valfs*4 Pathogenic Multiple CALMs. Brems (2007)
38643351 Exon 7 Missense c.821A>G p.Asp274Gly SuspectedBenign Brems (2012)
38643362 Exon 7 Frameshift c.832dupT p.Ser278Phefs*7 Pathogenic Brems (2012)  
38643396 Exon 7 Missense c.866A>C p.Lys289Thr Uncertain
38643453 Exon 7 Frameshift c.923_924delCT p.Ser308Cysfs*4 Pathogenic Multiple CALMs, head circumference: 25-50th and 97th percentile. Messiaen (2009)
38643456 Exon 7 Missense c.926T>C p.Val309Ala Benign Multiple CALMs. Spencer (2011)
38643461 Exon 7 Missense c.931T>C p.Phe311Leu Uncertain Messiaen
38643468 Exon 7 Missense c.938C>T p.Thr313Met Benign Multiple CALMs. Messiaen (2009)
38643469 Exon 7 Synonymous c.939G>A p.= Benign
38643470 Exon 7 Nonsense c.940C>T p.Gln314* Pathogenic Multiple CALMs, axillary and inguinal freckling, macrocephaly and mild learning disability. Denayer (2010)
38643474 Exon 7 Missense c.944C>T p.Pro315Leu SuspectedBenign Brems (2012)
38643493 Exon 7 Synonymous c.963G>A p.= Benign
38643494 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)
38643503 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)
38643519 Exon 7 Frameshift c.989delG p.Gly330Valfs*76 Pathogenic Brems (2012)  
38643521 Exon 7 Nonsense c.991G>T p.Glu331* Pathogenic Multiple CALMs. Spencer (2011)  
38643531 Exon 7 Missense c.1001G>A p.Arg334His Uncertain
38643536 Exon 7 Missense c.1006G>A p.Val336Ile Uncertain
38643561 Exon 7 Missense c.1031A>G p.His344Arg Uncertain Multiple CALMs. Spencer (2011)
38643574 Exon 7 Synonymous c.1044T>C p.Val348Val Benign Muram-Zborovski (2010)
38643575 Exon 7 Frameshift c.1045_1046delAG p.Arg349Glyfs*11 Pathogenic Multiple CALMs, general and inguinal freckling, macrocephaly, suspected autism. Denayer (2010)
38643577 Exon 7 Frameshift c.1048_1049delGG p.Gly350Lysfs*10 Pathogenic Multiple CALMs and freckling. Spurlock (2009)
38643578 Exon 7 Frameshift c.1048_1060del p.Gly350Metfs*52 Pathogenic Multiple CALMs, diffuse freckling (Pasamant). Multiple CALMs, macrocephaly, ADHD and lipomas (Denayer). Pasmant (2009)
38643579 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)
38643608 Exon 7 Missense c.1078A>G p.Lys360Glu Uncertain
38643609 Exon 7 Frameshift c.1073delC p.Pro358Leufs*48 Pathogenic Multiple CALMs. Spencer (2011)
38643619 Exon 7 Missense c.1089G>A p.Ile363Met Uncertain No signs of Legius syndrome; has B-cell acute lymphoblastic leukaemia Pasmant (2014)
38643626 Exon 7 Missense c.1096G>A p.Val366Ile Uncertain
38643685 Exon 7 Deletion c.1155del p.Gly385Ile*20 Pathogenic Legius syndrome Brems (2013)
38643722 Exon 7 Missense c.1192G>A p.Asp398Asn Benign Multiple CALMs (Spencer 2011). Multiple CALMs and hyperactivity (Messiaen). Messiaen (2009)
38643734 Exon 7 Frameshift c.1204_1207dupTTGC p.Arg403Leufs*30 Pathogenic Multiple CALMs and head circumference 90th percentile. Messiaen (2009)
38643752 Exon 7 Missense c.1222G>T p.Val408Leu Uncertain
38643753 Exon 7 Missense c.1223T>A p.Val408Glu Uncertain Brems (2012)
38643773 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)
38643776 Exon 7 Missense c.1246C>T p.Cys416Arg Uncertain Multiple CALMs. Spencer (2011)
38643778 Exon 7 Frameshift c.1248dupT p.Met417Tyrfs*15 Suspected Pathogenic Multiple CALMs and inguinal freckling. Messiaen (2009)
38643782 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)
38643790 Exon 7 Synonymous c.1260C>T p.= Benign
38643803 Exon 7 Missense c.1273A>G p.Met425Val Uncertain Legius syndrome Brems (2012)
38643813 Exon 7 Missense c.1283G>A p.Arg428His Uncertain
38643819 Exon 7 Missense c.1289G>C p.Gly430Ala Uncertain Brems (2012)
38643819 Exon 7 Frameshift c.1289_1298del p.Gly430Valfs*29 Uncertain Brems (2012)
38643828 Exon 7 Missense c.1298G>A p.Cys433Tyr Benign Messiaen (2009)