TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15239	45940;45941;45942	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
N2AB	13598	41017;41018;41019	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
N2A	12671	38236;38237;38238	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
N2B	6174	18745;18746;18747	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
Novex-1	6299	19120;19121;19122	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
Novex-2	6366	19321;19322;19323	chr2:178620895;178620894;178620893	chr2:179485622;179485621;179485620
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-104
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.3702
• 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/N	None	None	1.0	D	0.757	0.446	0.345405024496	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
K/A	0.7139	likely_pathogenic	0.7579	pathogenic	-0.33	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
K/C	0.8992	likely_pathogenic	0.9156	pathogenic	-0.484	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/D	0.8924	likely_pathogenic	0.9107	pathogenic	0.121	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/E	0.4264	ambiguous	0.5042	ambiguous	0.194	Stabilizing	0.999	D	0.603	neutral	N	0.50421281	None	None	N
K/F	0.9417	likely_pathogenic	0.95	pathogenic	-0.269	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/G	0.8427	likely_pathogenic	0.8639	pathogenic	-0.609	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/H	0.5522	ambiguous	0.5992	pathogenic	-0.761	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/I	0.6172	likely_pathogenic	0.6591	pathogenic	0.355	Stabilizing	1.0	D	0.825	deleterious	D	0.541123585	None	None	N
K/L	0.6717	likely_pathogenic	0.6888	pathogenic	0.355	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/M	0.5172	ambiguous	0.5537	ambiguous	0.022	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/N	0.7336	likely_pathogenic	0.7681	pathogenic	-0.152	Destabilizing	1.0	D	0.757	deleterious	D	0.653190758	None	None	N
K/P	0.9821	likely_pathogenic	0.9825	pathogenic	0.156	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/Q	0.2453	likely_benign	0.3038	benign	-0.21	Destabilizing	1.0	D	0.743	deleterious	N	0.508607898	None	None	N
K/R	0.1071	likely_benign	0.1142	benign	-0.207	Destabilizing	0.999	D	0.554	neutral	N	0.509970291	None	None	N
K/S	0.7296	likely_pathogenic	0.7683	pathogenic	-0.728	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
K/T	0.4005	ambiguous	0.4478	ambiguous	-0.468	Destabilizing	1.0	D	0.765	deleterious	N	0.509603973	None	None	N
K/V	0.5591	ambiguous	0.6017	pathogenic	0.156	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/W	0.9403	likely_pathogenic	0.9473	pathogenic	-0.225	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/Y	0.8735	likely_pathogenic	0.8887	pathogenic	0.085	Stabilizing	1.0	D	0.791	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.