TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18289	55090;55091;55092	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
N2AB	16648	50167;50168;50169	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
N2A	15721	47386;47387;47388	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
N2B	9224	27895;27896;27897	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
Novex-1	9349	28270;28271;28272	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
Novex-2	9416	28471;28472;28473	chr2:178602537;178602536;178602535	chr2:179467264;179467263;179467262
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-21
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0781
• 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
I/M	None	None	0.81	D	0.672	0.193	0.434272847907	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
I/T	None	None	0.549	N	0.727	0.411	0.598386477769	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
I/A	0.8303	likely_pathogenic	0.739	pathogenic	-2.741	Highly Destabilizing	0.25	N	0.617	neutral	None	None	None	None	N
I/C	0.8888	likely_pathogenic	0.8396	pathogenic	-2.373	Highly Destabilizing	0.977	D	0.784	deleterious	None	None	None	None	N
I/D	0.9977	likely_pathogenic	0.997	pathogenic	-3.057	Highly Destabilizing	0.972	D	0.81	deleterious	None	None	None	None	N
I/E	0.994	likely_pathogenic	0.9934	pathogenic	-2.739	Highly Destabilizing	0.92	D	0.802	deleterious	None	None	None	None	N
I/F	0.632	likely_pathogenic	0.5304	ambiguous	-1.668	Destabilizing	0.81	D	0.724	prob.delet.	N	0.489512719	None	None	N
I/G	0.9864	likely_pathogenic	0.9735	pathogenic	-3.375	Highly Destabilizing	0.766	D	0.779	deleterious	None	None	None	None	N
I/H	0.9893	likely_pathogenic	0.9823	pathogenic	-3.011	Highly Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
I/K	0.9894	likely_pathogenic	0.9877	pathogenic	-2.037	Highly Destabilizing	0.92	D	0.803	deleterious	None	None	None	None	N
I/L	0.2994	likely_benign	0.2285	benign	-0.852	Destabilizing	0.045	N	0.515	neutral	N	0.475319883	None	None	N
I/M	0.3843	ambiguous	0.3507	ambiguous	-1.18	Destabilizing	0.81	D	0.672	neutral	D	0.523754123	None	None	N
I/N	0.9697	likely_pathogenic	0.9621	pathogenic	-2.651	Highly Destabilizing	0.963	D	0.815	deleterious	N	0.515178299	None	None	N
I/P	0.9965	likely_pathogenic	0.9941	pathogenic	-1.47	Destabilizing	0.972	D	0.814	deleterious	None	None	None	None	N
I/Q	0.9869	likely_pathogenic	0.9843	pathogenic	-2.317	Highly Destabilizing	0.972	D	0.809	deleterious	None	None	None	None	N
I/R	0.9779	likely_pathogenic	0.971	pathogenic	-2.079	Highly Destabilizing	0.92	D	0.812	deleterious	None	None	None	None	N
I/S	0.9323	likely_pathogenic	0.907	pathogenic	-3.377	Highly Destabilizing	0.549	D	0.767	deleterious	N	0.503150431	None	None	N
I/T	0.9173	likely_pathogenic	0.8625	pathogenic	-2.877	Highly Destabilizing	0.549	D	0.727	prob.delet.	N	0.502896941	None	None	N
I/V	0.0953	likely_benign	0.0738	benign	-1.47	Destabilizing	0.001	N	0.19	neutral	N	0.404193291	None	None	N
I/W	0.9914	likely_pathogenic	0.987	pathogenic	-1.997	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
I/Y	0.9521	likely_pathogenic	0.9321	pathogenic	-1.765	Destabilizing	0.92	D	0.815	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.