TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29522	88789;88790;88791	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
N2AB	27881	83866;83867;83868	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
N2A	26954	81085;81086;81087	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
N2B	20457	61594;61595;61596	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
Novex-1	20582	61969;61970;61971	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
Novex-2	20649	62170;62171;62172	chr2:178554895;178554894;178554893	chr2:179419622;179419621;179419620
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-146
• Domain position: 79
• Structural Position: 166
• Q(SASA): 0.4609
• 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
A/G	None	None	0.998	N	0.609	0.402	0.583959843308	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
A/C	0.5422	ambiguous	0.5345	ambiguous	-0.853	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
A/D	0.4521	ambiguous	0.4349	ambiguous	-0.224	Destabilizing	0.999	D	0.823	deleterious	N	0.460794014	None	None	I
A/E	0.4234	ambiguous	0.3947	ambiguous	-0.364	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
A/F	0.5355	ambiguous	0.5229	ambiguous	-0.749	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
A/G	0.2633	likely_benign	0.2438	benign	-0.229	Destabilizing	0.998	D	0.609	neutral	N	0.489254863	None	None	I
A/H	0.613	likely_pathogenic	0.5942	pathogenic	-0.222	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
A/I	0.3596	ambiguous	0.3408	ambiguous	-0.259	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	I
A/K	0.5261	ambiguous	0.4815	ambiguous	-0.534	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
A/L	0.3665	ambiguous	0.346	ambiguous	-0.259	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	I
A/M	0.3485	ambiguous	0.3364	benign	-0.452	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/N	0.4327	ambiguous	0.4273	ambiguous	-0.286	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
A/P	0.9716	likely_pathogenic	0.9673	pathogenic	-0.202	Destabilizing	1.0	D	0.827	deleterious	N	0.489508353	None	None	I
A/Q	0.4433	ambiguous	0.4193	ambiguous	-0.509	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
A/R	0.4844	ambiguous	0.4396	ambiguous	-0.14	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
A/S	0.1198	likely_benign	0.1207	benign	-0.521	Destabilizing	0.992	D	0.546	neutral	N	0.5058543	None	None	I
A/T	0.091	likely_benign	0.0889	benign	-0.572	Destabilizing	0.884	D	0.369	neutral	N	0.51435914	None	None	I
A/V	0.1599	likely_benign	0.153	benign	-0.202	Destabilizing	0.996	D	0.617	neutral	N	0.484169519	None	None	I
A/W	0.9087	likely_pathogenic	0.9022	pathogenic	-0.89	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
A/Y	0.6627	likely_pathogenic	0.6551	pathogenic	-0.544	Destabilizing	1.0	D	0.836	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.