TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22059	66400;66401;66402	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
N2AB	20418	61477;61478;61479	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
N2A	19491	58696;58697;58698	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
N2B	12994	39205;39206;39207	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
Novex-1	13119	39580;39581;39582	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
Novex-2	13186	39781;39782;39783	chr2:178582194;178582193;178582192	chr2:179446921;179446920;179446919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-48
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.108
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
C/S	None	None	0.078	N	0.461	0.316	0.299086750705	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
C/A	0.7176	likely_pathogenic	0.6261	pathogenic	-1.113	Destabilizing	0.373	N	0.533	neutral	None	None	None	None	N
C/D	0.9965	likely_pathogenic	0.9944	pathogenic	-1.691	Destabilizing	0.91	D	0.695	prob.neutral	None	None	None	None	N
C/E	0.9987	likely_pathogenic	0.9981	pathogenic	-1.556	Destabilizing	0.91	D	0.693	prob.neutral	None	None	None	None	N
C/F	0.9765	likely_pathogenic	0.9528	pathogenic	-0.872	Destabilizing	0.979	D	0.717	prob.delet.	N	0.462171164	None	None	N
C/G	0.7623	likely_pathogenic	0.6189	pathogenic	-1.389	Destabilizing	0.684	D	0.639	neutral	N	0.461917675	None	None	N
C/H	0.9968	likely_pathogenic	0.994	pathogenic	-1.926	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
C/I	0.9319	likely_pathogenic	0.9086	pathogenic	-0.417	Destabilizing	0.953	D	0.695	prob.neutral	None	None	None	None	N
C/K	0.9995	likely_pathogenic	0.9992	pathogenic	-0.96	Destabilizing	0.91	D	0.693	prob.neutral	None	None	None	None	N
C/L	0.9234	likely_pathogenic	0.8972	pathogenic	-0.417	Destabilizing	0.742	D	0.61	neutral	None	None	None	None	N
C/M	0.9704	likely_pathogenic	0.9645	pathogenic	0.432	Stabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	N
C/N	0.9838	likely_pathogenic	0.9775	pathogenic	-1.28	Destabilizing	0.91	D	0.704	prob.neutral	None	None	None	None	N
C/P	0.3899	ambiguous	0.4045	ambiguous	-0.624	Destabilizing	0.009	N	0.571	neutral	None	None	None	None	N
C/Q	0.997	likely_pathogenic	0.9951	pathogenic	-1.124	Destabilizing	0.953	D	0.743	deleterious	None	None	None	None	N
C/R	0.9963	likely_pathogenic	0.993	pathogenic	-1.152	Destabilizing	0.939	D	0.738	prob.delet.	N	0.462171164	None	None	N
C/S	0.8237	likely_pathogenic	0.7528	pathogenic	-1.44	Destabilizing	0.078	N	0.461	neutral	N	0.505373432	None	None	N
C/T	0.8923	likely_pathogenic	0.8663	pathogenic	-1.161	Destabilizing	0.742	D	0.606	neutral	None	None	None	None	N
C/V	0.7983	likely_pathogenic	0.7718	pathogenic	-0.624	Destabilizing	0.854	D	0.641	neutral	None	None	None	None	N
C/W	0.997	likely_pathogenic	0.9939	pathogenic	-1.287	Destabilizing	0.994	D	0.725	prob.delet.	N	0.462424654	None	None	N
C/Y	0.9949	likely_pathogenic	0.9876	pathogenic	-0.992	Destabilizing	0.979	D	0.721	prob.delet.	N	0.462171164	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.