TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19970	60133;60134;60135	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
N2AB	18329	55210;55211;55212	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
N2A	17402	52429;52430;52431	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
N2B	10905	32938;32939;32940	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
Novex-1	11030	33313;33314;33315	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
Novex-2	11097	33514;33515;33516	chr2:178591996;178591995;178591994	chr2:179456723;179456722;179456721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-32
• Domain position: 94
• Structural Position: 128
• Q(SASA): 0.4265
• 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
K/E	None	None	0.997	N	0.839	0.264	0.315609569513	gnomAD-4.0.0	1.59358E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86085E-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
K/A	0.5921	likely_pathogenic	0.586	pathogenic	-0.218	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
K/C	0.8156	likely_pathogenic	0.8237	pathogenic	-0.389	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/D	0.877	likely_pathogenic	0.8828	pathogenic	0.229	Stabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
K/E	0.405	ambiguous	0.408	ambiguous	0.283	Stabilizing	0.997	D	0.839	deleterious	N	0.467184367	None	None	N
K/F	0.8707	likely_pathogenic	0.8811	pathogenic	-0.166	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/G	0.8313	likely_pathogenic	0.8343	pathogenic	-0.499	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.4846	ambiguous	0.4719	ambiguous	-0.743	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/I	0.4216	ambiguous	0.4418	ambiguous	0.466	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
K/L	0.3856	ambiguous	0.3994	ambiguous	0.466	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/M	0.3013	likely_benign	0.3082	benign	0.252	Stabilizing	1.0	D	0.735	deleterious	N	0.514763706	None	None	N
K/N	0.7424	likely_pathogenic	0.7471	pathogenic	-0.024	Destabilizing	0.999	D	0.763	deleterious	N	0.514763706	None	None	N
K/P	0.825	likely_pathogenic	0.8173	pathogenic	0.269	Stabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
K/Q	0.2232	likely_benign	0.2149	benign	-0.161	Destabilizing	0.999	D	0.77	deleterious	N	0.495735228	None	None	N
K/R	0.0971	likely_benign	0.0966	benign	-0.211	Destabilizing	0.997	D	0.766	deleterious	N	0.467437856	None	None	N
K/S	0.7499	likely_pathogenic	0.7411	pathogenic	-0.648	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
K/T	0.2893	likely_benign	0.2708	benign	-0.414	Destabilizing	0.999	D	0.767	deleterious	N	0.4800537	None	None	N
K/V	0.3909	ambiguous	0.3935	ambiguous	0.269	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/W	0.8568	likely_pathogenic	0.8728	pathogenic	-0.083	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Y	0.7594	likely_pathogenic	0.7778	pathogenic	0.235	Stabilizing	1.0	D	0.795	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.