TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2152	6679;6680;6681	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
N2AB	2152	6679;6680;6681	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
N2A	2152	6679;6680;6681	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
N2B	2106	6541;6542;6543	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
Novex-1	2106	6541;6542;6543	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
Novex-2	2106	6541;6542;6543	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135
Novex-3	2152	6679;6680;6681	chr2:178775410;178775409;178775408	chr2:179640137;179640136;179640135

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-10
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.1896
• Predicted PPI site: I

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/Q	None	None	1.0	N	0.817	0.458	0.357724736475	gnomAD-4.0.0	1.59064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85649E-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	0.9409	likely_pathogenic	0.951	pathogenic	-0.981	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
K/C	0.9614	likely_pathogenic	0.9629	pathogenic	-1.169	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
K/D	0.985	likely_pathogenic	0.9875	pathogenic	-1.112	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
K/E	0.8112	likely_pathogenic	0.84	pathogenic	-0.921	Destabilizing	0.999	D	0.669	neutral	N	0.5085053	None	None	I
K/F	0.9924	likely_pathogenic	0.9934	pathogenic	-0.434	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	I
K/G	0.9755	likely_pathogenic	0.9782	pathogenic	-1.421	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
K/H	0.7025	likely_pathogenic	0.7329	pathogenic	-1.752	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
K/I	0.9045	likely_pathogenic	0.9202	pathogenic	0.211	Stabilizing	1.0	D	0.921	deleterious	N	0.503632552	None	None	I
K/L	0.8956	likely_pathogenic	0.9021	pathogenic	0.211	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
K/M	0.794	likely_pathogenic	0.8173	pathogenic	0.035	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
K/N	0.9403	likely_pathogenic	0.9505	pathogenic	-1.298	Destabilizing	1.0	D	0.823	deleterious	N	0.508130827	None	None	I
K/P	0.9986	likely_pathogenic	0.9986	pathogenic	-0.159	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
K/Q	0.5259	ambiguous	0.5713	pathogenic	-1.212	Destabilizing	1.0	D	0.817	deleterious	N	0.511665423	None	None	I
K/R	0.1413	likely_benign	0.1498	benign	-1.093	Destabilizing	0.999	D	0.638	neutral	N	0.474190997	None	None	I
K/S	0.9473	likely_pathogenic	0.9574	pathogenic	-1.882	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
K/T	0.7246	likely_pathogenic	0.7811	pathogenic	-1.457	Destabilizing	1.0	D	0.849	deleterious	N	0.498012396	None	None	I
K/V	0.8532	likely_pathogenic	0.8733	pathogenic	-0.159	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
K/W	0.984	likely_pathogenic	0.9874	pathogenic	-0.398	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
K/Y	0.975	likely_pathogenic	0.9788	pathogenic	-0.062	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I

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.