TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27956	84091;84092;84093	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
N2AB	26315	79168;79169;79170	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
N2A	25388	76387;76388;76389	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
N2B	18891	56896;56897;56898	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
Novex-1	19016	57271;57272;57273	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
Novex-2	19083	57472;57473;57474	chr2:178562266;178562265;178562264	chr2:179426993;179426992;179426991
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-91
• Domain position: 94
• Structural Position: 130
• Q(SASA): 0.0731
• 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
A/S	None	None	0.989	D	0.614	0.413	0.455816718377	gnomAD-4.0.0	2.05323E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69877E-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	0.6907	likely_pathogenic	0.7073	pathogenic	-1.672	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/D	0.9962	likely_pathogenic	0.9977	pathogenic	-2.563	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/E	0.9882	likely_pathogenic	0.9924	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.733	deleterious	N	0.51856993	None	None	N
A/F	0.9518	likely_pathogenic	0.9665	pathogenic	-0.941	Destabilizing	0.997	D	0.788	deleterious	None	None	None	None	N
A/G	0.5775	likely_pathogenic	0.6335	pathogenic	-1.677	Destabilizing	0.797	D	0.566	neutral	N	0.51907691	None	None	N
A/H	0.9932	likely_pathogenic	0.9954	pathogenic	-1.822	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/I	0.6002	likely_pathogenic	0.6339	pathogenic	-0.248	Destabilizing	0.992	D	0.685	prob.delet.	None	None	None	None	N
A/K	0.9949	likely_pathogenic	0.9966	pathogenic	-1.287	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	N
A/L	0.6479	likely_pathogenic	0.7015	pathogenic	-0.248	Destabilizing	0.98	D	0.601	neutral	None	None	None	None	N
A/M	0.8099	likely_pathogenic	0.8556	pathogenic	-0.672	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/N	0.9774	likely_pathogenic	0.984	pathogenic	-1.565	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
A/P	0.7078	likely_pathogenic	0.7643	pathogenic	-0.553	Destabilizing	1.0	D	0.779	deleterious	N	0.480969069	None	None	N
A/Q	0.9747	likely_pathogenic	0.9812	pathogenic	-1.49	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
A/R	0.9806	likely_pathogenic	0.986	pathogenic	-1.247	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/S	0.3351	likely_benign	0.3673	ambiguous	-1.954	Destabilizing	0.989	D	0.614	neutral	D	0.529419257	None	None	N
A/T	0.4373	ambiguous	0.4889	ambiguous	-1.694	Destabilizing	0.998	D	0.622	neutral	N	0.492614862	None	None	N
A/V	0.354	ambiguous	0.3909	ambiguous	-0.553	Destabilizing	0.183	N	0.31	neutral	N	0.489281763	None	None	N
A/W	0.9962	likely_pathogenic	0.9972	pathogenic	-1.528	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.9881	likely_pathogenic	0.992	pathogenic	-1.054	Destabilizing	1.0	D	0.783	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.