TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20765	62518;62519;62520	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
N2AB	19124	57595;57596;57597	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
N2A	18197	54814;54815;54816	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
N2B	11700	35323;35324;35325	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
Novex-1	11825	35698;35699;35700	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
Novex-2	11892	35899;35900;35901	chr2:178589432;178589431;178589430	chr2:179454159;179454158;179454157
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: Fn3-38
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.9013
• 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/A	None	None	0.799	N	0.529	0.257	0.365703291355	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
D/A	0.3718	ambiguous	0.4704	ambiguous	-0.157	Destabilizing	0.799	D	0.529	neutral	N	0.434818134	None	None	N
D/C	0.8846	likely_pathogenic	0.9405	pathogenic	-0.026	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
D/E	0.1968	likely_benign	0.281	benign	-0.255	Destabilizing	0.005	N	0.195	neutral	N	0.361048307	None	None	N
D/F	0.7964	likely_pathogenic	0.8708	pathogenic	-0.118	Destabilizing	0.974	D	0.661	prob.neutral	None	None	None	None	N
D/G	0.4646	ambiguous	0.5658	pathogenic	-0.329	Destabilizing	0.799	D	0.499	neutral	N	0.478704984	None	None	N
D/H	0.6625	likely_pathogenic	0.751	pathogenic	0.18	Stabilizing	0.966	D	0.525	neutral	N	0.46046594	None	None	N
D/I	0.532	ambiguous	0.6497	pathogenic	0.239	Stabilizing	0.903	D	0.577	neutral	None	None	None	None	N
D/K	0.7256	likely_pathogenic	0.8033	pathogenic	0.374	Stabilizing	0.725	D	0.492	neutral	None	None	None	None	N
D/L	0.5776	likely_pathogenic	0.6839	pathogenic	0.239	Stabilizing	0.725	D	0.596	neutral	None	None	None	None	N
D/M	0.7583	likely_pathogenic	0.8413	pathogenic	0.225	Stabilizing	0.993	D	0.615	neutral	None	None	None	None	N
D/N	0.2254	likely_benign	0.2932	benign	0.096	Stabilizing	0.799	D	0.557	neutral	N	0.477838193	None	None	N
D/P	0.7976	likely_pathogenic	0.8249	pathogenic	0.128	Stabilizing	0.974	D	0.615	neutral	None	None	None	None	N
D/Q	0.5955	likely_pathogenic	0.6865	pathogenic	0.12	Stabilizing	0.903	D	0.463	neutral	None	None	None	None	N
D/R	0.7829	likely_pathogenic	0.8347	pathogenic	0.564	Stabilizing	0.949	D	0.63	neutral	None	None	None	None	N
D/S	0.3348	likely_benign	0.4226	ambiguous	-0.006	Destabilizing	0.841	D	0.464	neutral	None	None	None	None	N
D/T	0.4509	ambiguous	0.5452	ambiguous	0.129	Stabilizing	0.841	D	0.625	neutral	None	None	None	None	N
D/V	0.3514	ambiguous	0.4592	ambiguous	0.128	Stabilizing	0.051	N	0.389	neutral	N	0.412250706	None	None	N
D/W	0.9599	likely_pathogenic	0.9721	pathogenic	-0.011	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
D/Y	0.503	ambiguous	0.612	pathogenic	0.117	Stabilizing	0.989	D	0.662	prob.neutral	N	0.479398418	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.