TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16520	49783;49784;49785	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
N2AB	14879	44860;44861;44862	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
N2A	13952	42079;42080;42081	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
N2B	7455	22588;22589;22590	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
Novex-1	7580	22963;22964;22965	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
Novex-2	7647	23164;23165;23166	chr2:178613251;178613250;178613249	chr2:179477978;179477977;179477976
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: Fn3-7
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.579
• 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	rs779658426	-1.194	1.0	N	0.724	0.254	0.187945064343	gnomAD-2.1.1	5.69E-05	None	None	None	None	N	None	0	4.10654E-04	None	0	0	None	0	None	0	0	0
K/N	rs779658426	-1.194	1.0	N	0.724	0.254	0.187945064343	gnomAD-4.0.0	2.26238E-05	None	None	None	None	N	None	0	3.14861E-04	None	0	0	None	0	0	1.53058E-05	0	3.32127E-05

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	0.7847	likely_pathogenic	0.5494	ambiguous	-0.533	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
K/C	0.9157	likely_pathogenic	0.759	pathogenic	-0.697	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/D	0.9416	likely_pathogenic	0.8492	pathogenic	-0.069	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.7225	likely_pathogenic	0.399	ambiguous	0.076	Stabilizing	0.999	D	0.64	neutral	N	0.409903678	None	None	N
K/F	0.9555	likely_pathogenic	0.8822	pathogenic	-0.167	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/G	0.8727	likely_pathogenic	0.7378	pathogenic	-0.89	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/H	0.6591	likely_pathogenic	0.4609	ambiguous	-0.885	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/I	0.7374	likely_pathogenic	0.4809	ambiguous	0.398	Stabilizing	1.0	D	0.776	deleterious	N	0.480605805	None	None	N
K/L	0.6954	likely_pathogenic	0.4891	ambiguous	0.398	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/M	0.5381	ambiguous	0.2938	benign	-0.046	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/N	0.8202	likely_pathogenic	0.6468	pathogenic	-0.585	Destabilizing	1.0	D	0.724	prob.delet.	N	0.4802259	None	None	N
K/P	0.8408	likely_pathogenic	0.6921	pathogenic	0.116	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/Q	0.4023	ambiguous	0.199	benign	-0.512	Destabilizing	1.0	D	0.705	prob.neutral	N	0.47132027	None	None	N
K/R	0.1354	likely_benign	0.1054	benign	-0.377	Destabilizing	0.999	D	0.569	neutral	N	0.481222935	None	None	N
K/S	0.8328	likely_pathogenic	0.6368	pathogenic	-1.184	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
K/T	0.4987	ambiguous	0.2522	benign	-0.826	Destabilizing	1.0	D	0.763	deleterious	N	0.462587948	None	None	N
K/V	0.6977	likely_pathogenic	0.435	ambiguous	0.116	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/W	0.9341	likely_pathogenic	0.8335	pathogenic	-0.123	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
K/Y	0.8673	likely_pathogenic	0.7193	pathogenic	0.171	Stabilizing	1.0	D	0.743	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.