TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14950	45073;45074;45075	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
N2AB	13309	40150;40151;40152	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
N2A	12382	37369;37370;37371	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
N2B	5885	17878;17879;17880	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
Novex-1	6010	18253;18254;18255	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
Novex-2	6077	18454;18455;18456	chr2:178622735;178622734;178622733	chr2:179487462;179487461;179487460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-101
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.853
• 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
D/E	rs371376631	0.076	0.992	D	0.402	0.271	0.224531998449	gnomAD-2.1.1	1.26E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.04588E-04	None	0	0	0
D/E	rs371376631	0.076	0.992	D	0.402	0.271	0.224531998449	gnomAD-4.0.0	2.06356E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.54845E-05	0
D/G	rs1194581912	0.027	0.992	D	0.6	0.406	0.299770980665	gnomAD-2.1.1	4.19E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.73E-05	0	0
D/G	rs1194581912	0.027	0.992	D	0.6	0.406	0.299770980665	gnomAD-4.0.0	1.61074E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89459E-05	0	0	0	0
D/H	rs571524382	None	1.0	D	0.653	0.389	None	gnomAD-3.1.2	6.6E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
D/H	rs571524382	None	1.0	D	0.653	0.389	None	gnomAD-4.0.0	1.2461E-06	None	None	None	None	N	None	2.68248E-05	0	None	0	0	None	0	0	0	0	0
D/N	rs571524382	0.493	0.999	N	0.619	0.36	0.267755039894	gnomAD-2.1.1	2.6E-05	None	None	None	None	N	None	8.69E-05	0	None	0	5.33E-05	None	0	None	0	3.24E-05	0
D/N	rs571524382	0.493	0.999	N	0.619	0.36	0.267755039894	gnomAD-3.1.2	6.6E-05	None	None	None	None	N	None	1.45229E-04	0	0	0	1.95084E-04	None	0	0	4.42E-05	0	0
D/N	rs571524382	0.493	0.999	N	0.619	0.36	0.267755039894	1000 genomes	3.99361E-04	None	None	None	None	N	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
D/N	rs571524382	0.493	0.999	N	0.619	0.36	0.267755039894	gnomAD-4.0.0	2.24281E-05	None	None	None	None	N	None	1.47295E-04	0	None	0	4.50714E-05	None	0	0	1.95613E-05	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
D/A	0.6044	likely_pathogenic	0.6809	pathogenic	-0.18	Destabilizing	0.984	D	0.564	neutral	D	0.541843204	None	None	N
D/C	0.9478	likely_pathogenic	0.9599	pathogenic	0.01	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
D/E	0.5956	likely_pathogenic	0.6561	pathogenic	-0.204	Destabilizing	0.992	D	0.402	neutral	D	0.545166353	None	None	N
D/F	0.9435	likely_pathogenic	0.9672	pathogenic	-0.097	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/G	0.5617	ambiguous	0.6207	pathogenic	-0.369	Destabilizing	0.992	D	0.6	neutral	D	0.67545156	None	None	N
D/H	0.7256	likely_pathogenic	0.7891	pathogenic	0.19	Stabilizing	1.0	D	0.653	neutral	D	0.580408306	None	None	N
D/I	0.9087	likely_pathogenic	0.9405	pathogenic	0.267	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
D/K	0.8841	likely_pathogenic	0.9179	pathogenic	0.368	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
D/L	0.8921	likely_pathogenic	0.9247	pathogenic	0.267	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
D/M	0.9634	likely_pathogenic	0.9762	pathogenic	0.284	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/N	0.2279	likely_benign	0.2835	benign	0.078	Stabilizing	0.999	D	0.619	neutral	N	0.455734976	None	None	N
D/P	0.8238	likely_pathogenic	0.8886	pathogenic	0.14	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
D/Q	0.8657	likely_pathogenic	0.8976	pathogenic	0.117	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
D/R	0.8816	likely_pathogenic	0.9085	pathogenic	0.583	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/S	0.3668	ambiguous	0.436	ambiguous	-0.041	Destabilizing	0.935	D	0.362	neutral	None	None	None	None	N
D/T	0.7566	likely_pathogenic	0.8133	pathogenic	0.109	Stabilizing	0.996	D	0.673	neutral	None	None	None	None	N
D/V	0.7808	likely_pathogenic	0.8371	pathogenic	0.14	Stabilizing	0.999	D	0.681	prob.neutral	D	0.568962704	None	None	N
D/W	0.9881	likely_pathogenic	0.9918	pathogenic	0.025	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
D/Y	0.6649	likely_pathogenic	0.7523	pathogenic	0.145	Stabilizing	1.0	D	0.659	neutral	D	0.679479781	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.