TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8771	26536;26537;26538	chr2:178714463;178714462;178714461	chr2:179579190;179579189;179579188
N2AB	8454	25585;25586;25587	chr2:178714463;178714462;178714461	chr2:179579190;179579189;179579188
N2A	7527	22804;22805;22806	chr2:178714463;178714462;178714461	chr2:179579190;179579189;179579188
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-73
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.251
• 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
K/R	None	None	0.93	N	0.491	0.337	0.277317399466	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85887E-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	0.7402	likely_pathogenic	0.8639	pathogenic	-0.846	Destabilizing	0.99	D	0.523	neutral	None	None	None	None	N
K/C	0.8269	likely_pathogenic	0.8986	pathogenic	-0.956	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/D	0.9359	likely_pathogenic	0.968	pathogenic	-0.354	Destabilizing	0.997	D	0.64	neutral	None	None	None	None	N
K/E	0.4517	ambiguous	0.6284	pathogenic	-0.234	Destabilizing	0.916	D	0.473	neutral	D	0.531260503	None	None	N
K/F	0.8786	likely_pathogenic	0.9323	pathogenic	-0.682	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.8339	likely_pathogenic	0.9135	pathogenic	-1.206	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
K/H	0.4537	ambiguous	0.5306	ambiguous	-1.598	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
K/I	0.5795	likely_pathogenic	0.7179	pathogenic	0.09	Stabilizing	0.979	D	0.74	deleterious	D	0.529993055	None	None	N
K/L	0.5248	ambiguous	0.671	pathogenic	0.09	Stabilizing	0.908	D	0.66	neutral	None	None	None	None	N
K/M	0.4021	ambiguous	0.5508	ambiguous	0.074	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/N	0.8024	likely_pathogenic	0.8899	pathogenic	-0.647	Destabilizing	0.998	D	0.547	neutral	N	0.512902758	None	None	N
K/P	0.9666	likely_pathogenic	0.9821	pathogenic	-0.193	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/Q	0.2054	likely_benign	0.2779	benign	-0.773	Destabilizing	0.254	N	0.316	neutral	N	0.478326863	None	None	N
K/R	0.0834	likely_benign	0.0885	benign	-0.653	Destabilizing	0.93	D	0.491	neutral	N	0.465699429	None	None	N
K/S	0.7858	likely_pathogenic	0.888	pathogenic	-1.381	Destabilizing	0.99	D	0.517	neutral	None	None	None	None	N
K/T	0.562	ambiguous	0.7283	pathogenic	-1.048	Destabilizing	0.994	D	0.633	neutral	N	0.501292963	None	None	N
K/V	0.6015	likely_pathogenic	0.74	pathogenic	-0.193	Destabilizing	0.963	D	0.654	neutral	None	None	None	None	N
K/W	0.8142	likely_pathogenic	0.8752	pathogenic	-0.519	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
K/Y	0.7853	likely_pathogenic	0.8573	pathogenic	-0.182	Destabilizing	0.99	D	0.718	prob.delet.	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.