TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22134	66625;66626;66627	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
N2AB	20493	61702;61703;61704	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
N2A	19566	58921;58922;58923	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
N2B	13069	39430;39431;39432	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
Novex-1	13194	39805;39806;39807	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
Novex-2	13261	40006;40007;40008	chr2:178581969;178581968;178581967	chr2:179446696;179446695;179446694
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-48
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1106
• 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
N/K	None	None	1.0	D	0.739	0.632	0.267755039894	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
N/A	0.9953	likely_pathogenic	0.9965	pathogenic	-0.249	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/C	0.9243	likely_pathogenic	0.9454	pathogenic	-0.351	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
N/D	0.993	likely_pathogenic	0.9933	pathogenic	-2.266	Highly Destabilizing	0.999	D	0.61	neutral	D	0.535527961	None	None	N
N/E	0.999	likely_pathogenic	0.9987	pathogenic	-2.098	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
N/F	0.9995	likely_pathogenic	0.9995	pathogenic	-0.277	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
N/G	0.9772	likely_pathogenic	0.9801	pathogenic	-0.543	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
N/H	0.976	likely_pathogenic	0.9763	pathogenic	-0.429	Destabilizing	1.0	D	0.777	deleterious	D	0.560179583	None	None	N
N/I	0.9958	likely_pathogenic	0.9967	pathogenic	0.482	Stabilizing	1.0	D	0.801	deleterious	D	0.560433072	None	None	N
N/K	0.9988	likely_pathogenic	0.9986	pathogenic	0.011	Stabilizing	1.0	D	0.739	prob.delet.	D	0.559165625	None	None	N
N/L	0.9814	likely_pathogenic	0.9829	pathogenic	0.482	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/M	0.9962	likely_pathogenic	0.9971	pathogenic	0.576	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
N/P	0.9971	likely_pathogenic	0.9975	pathogenic	0.267	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
N/Q	0.9979	likely_pathogenic	0.9977	pathogenic	-0.873	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/R	0.9963	likely_pathogenic	0.9949	pathogenic	-0.061	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
N/S	0.735	likely_pathogenic	0.7719	pathogenic	-0.768	Destabilizing	0.999	D	0.605	neutral	N	0.507193036	None	None	N
N/T	0.9568	likely_pathogenic	0.9643	pathogenic	-0.464	Destabilizing	0.999	D	0.699	prob.neutral	N	0.511406091	None	None	N
N/V	0.9937	likely_pathogenic	0.9948	pathogenic	0.267	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
N/W	0.9998	likely_pathogenic	0.9998	pathogenic	-0.444	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/Y	0.9964	likely_pathogenic	0.9964	pathogenic	0.094	Stabilizing	1.0	D	0.808	deleterious	D	0.560179583	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.