TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1871	5836;5837;5838	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
N2AB	1871	5836;5837;5838	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
N2A	1871	5836;5837;5838	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
N2B	1825	5698;5699;5700	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
Novex-1	1825	5698;5699;5700	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
Novex-2	1825	5698;5699;5700	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978
Novex-3	1871	5836;5837;5838	chr2:178776253;178776252;178776251	chr2:179640980;179640979;179640978

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-9
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5882
• 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
K/N	None	None	0.999	N	0.672	0.239	0.20549828249	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.821	likely_pathogenic	0.8302	pathogenic	-0.01	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	I
K/C	0.967	likely_pathogenic	0.9685	pathogenic	-0.153	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
K/D	0.9587	likely_pathogenic	0.959	pathogenic	-0.011	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/E	0.7757	likely_pathogenic	0.746	pathogenic	0.014	Stabilizing	0.996	D	0.531	neutral	N	0.469401489	None	None	I
K/F	0.9824	likely_pathogenic	0.98	pathogenic	-0.055	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/G	0.932	likely_pathogenic	0.9364	pathogenic	-0.254	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/H	0.7024	likely_pathogenic	0.7187	pathogenic	-0.526	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/I	0.816	likely_pathogenic	0.7857	pathogenic	0.565	Stabilizing	1.0	D	0.741	deleterious	N	0.516435349	None	None	I
K/L	0.8199	likely_pathogenic	0.8101	pathogenic	0.565	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/M	0.7748	likely_pathogenic	0.754	pathogenic	0.31	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
K/N	0.9065	likely_pathogenic	0.8934	pathogenic	0.166	Stabilizing	0.999	D	0.672	neutral	N	0.511621875	None	None	I
K/P	0.9793	likely_pathogenic	0.9845	pathogenic	0.403	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/Q	0.4868	ambiguous	0.4814	ambiguous	0.007	Stabilizing	0.999	D	0.661	neutral	N	0.502849283	None	None	I
K/R	0.1132	likely_benign	0.1183	benign	-0.131	Destabilizing	0.64	D	0.285	neutral	N	0.511965635	None	None	I
K/S	0.8895	likely_pathogenic	0.8784	pathogenic	-0.315	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	I
K/T	0.6634	likely_pathogenic	0.6373	pathogenic	-0.133	Destabilizing	0.999	D	0.695	prob.neutral	N	0.470825533	None	None	I
K/V	0.7199	likely_pathogenic	0.6952	pathogenic	0.403	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
K/W	0.9813	likely_pathogenic	0.9818	pathogenic	-0.049	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/Y	0.9613	likely_pathogenic	0.9616	pathogenic	0.275	Stabilizing	1.0	D	0.728	prob.delet.	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.