TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20525	61798;61799;61800	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
N2AB	18884	56875;56876;56877	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
N2A	17957	54094;54095;54096	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
N2B	11460	34603;34604;34605	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
Novex-1	11585	34978;34979;34980	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
Novex-2	11652	35179;35180;35181	chr2:178590152;178590151;178590150	chr2:179454879;179454878;179454877
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: Ig-121
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.3032
• 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
L/F	None	None	0.497	N	0.437	0.203	0.185906805712	gnomAD-4.0.0	1.59262E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86044E-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	0.3429	ambiguous	0.3665	ambiguous	-2.286	Highly Destabilizing	0.272	N	0.401	neutral	None	None	None	None	I
L/C	0.4427	ambiguous	0.4333	ambiguous	-1.327	Destabilizing	0.968	D	0.538	neutral	None	None	None	None	I
L/D	0.7589	likely_pathogenic	0.8087	pathogenic	-2.19	Highly Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	I
L/E	0.5044	ambiguous	0.5595	ambiguous	-2.086	Highly Destabilizing	0.726	D	0.701	prob.neutral	None	None	None	None	I
L/F	0.1507	likely_benign	0.1404	benign	-1.436	Destabilizing	0.497	N	0.437	neutral	N	0.485479028	None	None	I
L/G	0.591	likely_pathogenic	0.6814	pathogenic	-2.723	Highly Destabilizing	0.726	D	0.695	prob.neutral	None	None	None	None	I
L/H	0.3433	ambiguous	0.3566	ambiguous	-2.064	Highly Destabilizing	0.958	D	0.719	prob.delet.	N	0.495015308	None	None	I
L/I	0.0767	likely_benign	0.0682	benign	-1.078	Destabilizing	None	N	0.155	neutral	N	0.393278156	None	None	I
L/K	0.3666	ambiguous	0.4288	ambiguous	-1.79	Destabilizing	0.726	D	0.649	neutral	None	None	None	None	I
L/M	0.103	likely_benign	0.0871	benign	-0.789	Destabilizing	0.567	D	0.495	neutral	None	None	None	None	I
L/N	0.4068	ambiguous	0.4912	ambiguous	-1.729	Destabilizing	0.89	D	0.715	prob.delet.	None	None	None	None	I
L/P	0.6119	likely_pathogenic	0.7416	pathogenic	-1.456	Destabilizing	0.859	D	0.715	prob.delet.	N	0.486621517	None	None	I
L/Q	0.2917	likely_benign	0.3096	benign	-1.787	Destabilizing	0.89	D	0.662	neutral	None	None	None	None	I
L/R	0.3282	likely_benign	0.3859	ambiguous	-1.265	Destabilizing	0.667	D	0.656	neutral	D	0.527096364	None	None	I
L/S	0.413	ambiguous	0.4708	ambiguous	-2.364	Highly Destabilizing	0.726	D	0.6	neutral	None	None	None	None	I
L/T	0.2477	likely_benign	0.276	benign	-2.14	Highly Destabilizing	0.567	D	0.469	neutral	None	None	None	None	I
L/V	0.1074	likely_benign	0.0874	benign	-1.456	Destabilizing	0.02	N	0.349	neutral	N	0.447128497	None	None	I
L/W	0.3568	ambiguous	0.3378	benign	-1.697	Destabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	I
L/Y	0.3898	ambiguous	0.365	ambiguous	-1.467	Destabilizing	0.726	D	0.528	neutral	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.