TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30093	90502;90503;90504	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
N2AB	28452	85579;85580;85581	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
N2A	27525	82798;82799;82800	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
N2B	21028	63307;63308;63309	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
Novex-1	21153	63682;63683;63684	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
Novex-2	21220	63883;63884;63885	chr2:178552623;178552622;178552621	chr2:179417350;179417349;179417348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-107
• Domain position: 64
• Structural Position: 97
• Q(SASA): 0.1575
• 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
L/F	None	None	1.0	D	0.873	0.715	0.857714189017	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
L/A	0.8289	likely_pathogenic	0.76	pathogenic	-1.963	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
L/C	0.7353	likely_pathogenic	0.6526	pathogenic	-1.705	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/D	0.9938	likely_pathogenic	0.9896	pathogenic	-1.116	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/E	0.9563	likely_pathogenic	0.9224	pathogenic	-1.068	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/F	0.6545	likely_pathogenic	0.5753	pathogenic	-1.456	Destabilizing	1.0	D	0.873	deleterious	D	0.642688435	None	None	N
L/G	0.9454	likely_pathogenic	0.9142	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/H	0.9464	likely_pathogenic	0.908	pathogenic	-1.479	Destabilizing	1.0	D	0.755	deleterious	D	0.659515013	None	None	N
L/I	0.2873	likely_benign	0.2611	benign	-1.024	Destabilizing	0.999	D	0.833	deleterious	D	0.604300905	None	None	N
L/K	0.9617	likely_pathogenic	0.9389	pathogenic	-1.275	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/M	0.2627	likely_benign	0.2299	benign	-1.014	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/N	0.958	likely_pathogenic	0.9317	pathogenic	-1.205	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/P	0.9738	likely_pathogenic	0.9605	pathogenic	-1.308	Destabilizing	1.0	D	0.801	deleterious	D	0.659515013	None	None	N
L/Q	0.8551	likely_pathogenic	0.7595	pathogenic	-1.338	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/R	0.9392	likely_pathogenic	0.8977	pathogenic	-0.764	Destabilizing	1.0	D	0.809	deleterious	D	0.643495652	None	None	N
L/S	0.9489	likely_pathogenic	0.9154	pathogenic	-1.987	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/T	0.8455	likely_pathogenic	0.782	pathogenic	-1.805	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/V	0.2794	likely_benign	0.2481	benign	-1.308	Destabilizing	0.999	D	0.841	deleterious	D	0.595589371	None	None	N
L/W	0.9045	likely_pathogenic	0.8517	pathogenic	-1.465	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/Y	0.9207	likely_pathogenic	0.8811	pathogenic	-1.233	Destabilizing	1.0	D	0.813	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.