TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24306	73141;73142;73143	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
N2AB	22665	68218;68219;68220	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
N2A	21738	65437;65438;65439	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
N2B	15241	45946;45947;45948	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
Novex-1	15366	46321;46322;46323	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
Novex-2	15433	46522;46523;46524	chr2:178573216;178573215;178573214	chr2:179437943;179437942;179437941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-64
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0918
• 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
S/T	rs762318997	-1.109	0.969	N	0.711	0.379	0.26169431596	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.05E-06	0
S/T	rs762318997	-1.109	0.969	N	0.711	0.379	0.26169431596	gnomAD-4.0.0	1.60921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8938E-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
S/A	0.4377	ambiguous	0.4099	ambiguous	-0.696	Destabilizing	0.807	D	0.667	neutral	None	None	None	None	N
S/C	0.7178	likely_pathogenic	0.6662	pathogenic	-0.575	Destabilizing	0.999	D	0.759	deleterious	D	0.544181106	None	None	N
S/D	0.9863	likely_pathogenic	0.9863	pathogenic	-1.057	Destabilizing	0.976	D	0.743	deleterious	None	None	None	None	N
S/E	0.9959	likely_pathogenic	0.9948	pathogenic	-0.982	Destabilizing	0.976	D	0.756	deleterious	None	None	None	None	N
S/F	0.9938	likely_pathogenic	0.9917	pathogenic	-0.504	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
S/G	0.0944	likely_benign	0.1073	benign	-1.03	Destabilizing	0.02	N	0.428	neutral	N	0.420210388	None	None	N
S/H	0.9859	likely_pathogenic	0.9857	pathogenic	-1.481	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
S/I	0.9934	likely_pathogenic	0.9905	pathogenic	0.111	Stabilizing	0.997	D	0.873	deleterious	D	0.532571311	None	None	N
S/K	0.9987	likely_pathogenic	0.9987	pathogenic	-0.962	Destabilizing	0.976	D	0.755	deleterious	None	None	None	None	N
S/L	0.9605	likely_pathogenic	0.9412	pathogenic	0.111	Stabilizing	0.993	D	0.829	deleterious	None	None	None	None	N
S/M	0.9791	likely_pathogenic	0.972	pathogenic	0.249	Stabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
S/N	0.9543	likely_pathogenic	0.9528	pathogenic	-1.163	Destabilizing	0.939	D	0.741	deleterious	D	0.543167148	None	None	N
S/P	0.9887	likely_pathogenic	0.9852	pathogenic	-0.122	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
S/Q	0.993	likely_pathogenic	0.9923	pathogenic	-1.144	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
S/R	0.9974	likely_pathogenic	0.9969	pathogenic	-0.984	Destabilizing	0.991	D	0.796	deleterious	N	0.520708027	None	None	N
S/T	0.7136	likely_pathogenic	0.6692	pathogenic	-0.986	Destabilizing	0.969	D	0.711	prob.delet.	N	0.515655144	None	None	N
S/V	0.9876	likely_pathogenic	0.9825	pathogenic	-0.122	Destabilizing	0.993	D	0.856	deleterious	None	None	None	None	N
S/W	0.9955	likely_pathogenic	0.9938	pathogenic	-0.638	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
S/Y	0.9903	likely_pathogenic	0.9863	pathogenic	-0.333	Destabilizing	0.998	D	0.871	deleterious	None	None	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.