TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15232	45919;45920;45921	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
N2AB	13591	40996;40997;40998	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
N2A	12664	38215;38216;38217	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
N2B	6167	18724;18725;18726	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
Novex-1	6292	19099;19100;19101	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
Novex-2	6359	19300;19301;19302	chr2:178620916;178620915;178620914	chr2:179485643;179485642;179485641
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: Ig-104
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5496
• 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/D	None	None	0.999	N	0.529	0.495	0.542587012665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.8624	likely_pathogenic	0.7761	pathogenic	-0.472	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
N/C	0.9224	likely_pathogenic	0.8641	pathogenic	0.158	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
N/D	0.6047	likely_pathogenic	0.5208	ambiguous	0.272	Stabilizing	0.999	D	0.529	neutral	N	0.503429264	None	None	N
N/E	0.9652	likely_pathogenic	0.929	pathogenic	0.287	Stabilizing	0.999	D	0.625	neutral	None	None	None	None	N
N/F	0.9808	likely_pathogenic	0.9585	pathogenic	-0.566	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
N/G	0.8641	likely_pathogenic	0.7976	pathogenic	-0.712	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
N/H	0.781	likely_pathogenic	0.6644	pathogenic	-0.522	Destabilizing	1.0	D	0.638	neutral	D	0.550384142	None	None	N
N/I	0.8701	likely_pathogenic	0.7478	pathogenic	0.088	Stabilizing	1.0	D	0.723	prob.delet.	N	0.503429264	None	None	N
N/K	0.9789	likely_pathogenic	0.9485	pathogenic	0.047	Stabilizing	1.0	D	0.637	neutral	N	0.504083558	None	None	N
N/L	0.8741	likely_pathogenic	0.767	pathogenic	0.088	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
N/M	0.9234	likely_pathogenic	0.8509	pathogenic	0.287	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	N
N/P	0.9708	likely_pathogenic	0.945	pathogenic	-0.07	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
N/Q	0.9573	likely_pathogenic	0.915	pathogenic	-0.467	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
N/R	0.9736	likely_pathogenic	0.9397	pathogenic	0.076	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/S	0.2166	likely_benign	0.1874	benign	-0.397	Destabilizing	0.999	D	0.476	neutral	N	0.451497517	None	None	N
N/T	0.5477	ambiguous	0.454	ambiguous	-0.211	Destabilizing	0.999	D	0.617	neutral	N	0.503288164	None	None	N
N/V	0.8751	likely_pathogenic	0.7645	pathogenic	-0.07	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
N/W	0.9949	likely_pathogenic	0.988	pathogenic	-0.439	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
N/Y	0.8553	likely_pathogenic	0.7475	pathogenic	-0.205	Destabilizing	1.0	D	0.668	neutral	N	0.499148553	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.